Abstract
Gliomas are a deadly primary malignant tumor of the central nervous system, with glioblastoma (GBM) representing the most aggressive type. The clinical prognosis of GBM patients remains bleak despite the availability of multiple options for therapy, which has needed us to explore new therapeutic methods to face the rapid progression, short survival, and therapy resistance of glioblastomas. As the Human Genome Project advances, long noncoding RNAs (lncRNAs) have attracted the attention of researchers and clinicians in cancer research. Numerous studies have found aberrant expression of signaling pathways in glioma cells. For example, lncRNAs not only play an integral role in the drug resistance process by regulating the Wnt/β-catenin or PI3K/Akt signaling but are also involved in a variety of malignant biological behaviors such as glioma proliferation, migration, invasion, and tumor apoptosis. Therefore, the present review systematically assesses the existing research evidence on the malignant progression and drug resistance of glioma, focusing on the critical role and potential function of lncRNAs in the Wnt/β-catenin and PI3K/Akt classical pathways to promote and encourage further research in this field.
Similar content being viewed by others
Data Availability
This is a review article, and all information is listed in the manuscript.
References
Agosti E, Panciani PP, Zeppieri M, De Maria L, Pasqualetti F, Tel A, Zanin L, Fontanella MM, Ius T (2023) Tumor microenvironment and glioblastoma cell interplay as promoters of therapeutic resistance. Biology (Basel) 12:736
Akhave NS, Biter AB, Hong DS (2021) Mechanisms of Resistance to KRAS(G12C)-Targeted Therapy. Cancer Discov 11:1345–1352
Alves CL, Ditzel HJ (2023) Drugging the PI3K/AKT/mTOR pathway in ER+ breast cancer. Int J Mol Sci 24:4522
Ashrafizadeh M, Zarrabi A, Mostafavi E, Aref AR, Sethi G, Wang L, Tergaonkar V (2022) Non-coding RNA-based regulation of inflammation. Semin Immunol 59:101606
Babar IA, Cheng CJ, Booth CJ, Liang X, Weidhaas JB, Saltzman WM, Slack FJ (2012) Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma. Proc Natl Acad Sci U S A 109:E1695-1704
Bader AG, Kang S, Zhao L, Vogt PK (2005) Oncogenic PI3K deregulates transcription and translation. Nat Rev Cancer 5:921–929
Benetatos L, Voulgaris E, Vartholomatos G (2017) The crosstalk between long non-coding RNAs and PI3K in cancer. Med Oncol 34:39
Bianchi ME, Mezzapelle R (2020) The Chemokine Receptor CXCR4 in Cell Proliferation and Tissue Regeneration. Front Immunol 11:2109
Cao T, Cui Y, Wang Y, Wu L, Yu K, Chen K, Xia J, Li Y, Wang ZP, Ma J (2022) CACNA1C-AS2 inhibits cell proliferation and suppresses cell migration and invasion via targeting FBXO45 and PI3K/AKT/mTOR pathways in glioma. Apoptosis 27:979–991
Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, Tramontano A, Bozzoni I (2011) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147:358–369
Chai B, Ma Z, Wang X, Xu L, Li Y (2022) Functions of non-coding RNAs in regulating cancer drug targets. Acta Biochim Biophys Sin (shanghai) 54:279–291
Chandra Gupta S, Nandan Tripathi Y (2017) Potential of long non-coding RNAs in cancer patients: From biomarkers to therapeutic targets. Int J Cancer 140:1955–1967
Chen Q, Cai J, Wang Q, Wang Y, Liu M, Yang J, Zhou J, Kang C, Li M, Jiang C (2018) Long Noncoding RNA NEAT1, Regulated by the EGFR Pathway, Contributes to Glioblastoma Progression Through the WNT/β-Catenin Pathway by Scaffolding EZH2. Clin Cancer Res 24:684–695
Chen Q, Wang W, Wu Z, Chen S, Chen X, Zhuang S, Song G, Lv Y, Lin Y (2021) Over-expression of lncRNA TMEM161B-AS1 promotes the malignant biological behavior of glioma cells and the resistance to temozolomide via up-regulating the expression of multiple ferroptosis-related genes by sponging hsa-miR-27a-3p. Cell Death Discov 7:311
Cheng J, Meng J, Zhu L, Peng Y (2020a) Exosomal noncoding RNAs in Glioma: biological functions and potential clinical applications. Mol Cancer 19:66
Cheng Z, Luo C, Guo Z (2020b) LncRNA-XIST/microRNA-126 sponge mediates cell proliferation and glucose metabolism through the IRS1/PI3K/Akt pathway in glioma. J Cell Biochem 121:2170–2183
Choi HI, An GY, Yoo E, Baek M, Chai JC, Binas B, Lee YS, Jung KH, Chai YG (2022) Targeting of noncoding RNAs encoded by a novel MYC enhancers inhibits the proliferation of human hepatic carcinoma cells in vitro. Sci Rep 12:855
Curtin JC, Lorenzi MV (2010) Drug discovery approaches to target Wnt signaling in cancer stem cells. Oncotarget 1:563–577
Dahlmanns M, Yakubov E, Dahlmanns JK (2021) Genetic Profiles of Ferroptosis in Malignant Brain Tumors and Off-Target Effects of Ferroptosis Induction. Front Oncol 11:783067
Dai B, Xiao Z, Mao B, Zhu G, Huang H, Guan F, Su H, Lin Z, Peng W, Hu Z (2019) lncRNA AWPPH promotes the migration and invasion of glioma cells by activating the TGF-β pathway. Oncol Lett 18:5923–5929
Deveson IW, Hardwick SA, Mercer TR, Mattick JS (2017) The Dimensions, Dynamics, and Relevance of the Mammalian Noncoding Transcriptome. Trends Genet 33:464–478
Ding M, Xu Q, Jin X, Han Z, Jiang H, Sun H, Jin Y, Piao Z, Zhang S (2023) Novel exosome-related risk signature as prognostic biomarkers in glioblastoma. Front Immunol 14:1071023
Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:1060–1072
Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Röder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Bar NS, Batut P, Bell K, Bell I, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Falconnet E, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena H, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Luo OJ, Park E, Persaud K, Preall JB, Ribeca P, Risk B, Robyr D, Sammeth M, Schaffer L, See LH, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu Y, Ruan X, Hayashizaki Y, Harrow J, Gerstein M, Hubbard T, Reymond A, Antonarakis SE, Hannon G, Giddings MC, Ruan Y, Wold B, Carninci P, Guigó R, Gingeras TR (2012) Landscape of transcription in human cells. Nature 489:101–108
Du L, Lee JH, Jiang H, Wang C, Wang S, Zheng Z, Shao F, Xu D, Xia Y, Li J, Zheng Y, Qian X, Li X, Kim H.R, Xing D, Liu P, Lu Z, Lyu J (2020) β-Catenin induces transcriptional expression of PD-L1 to promote glioblastoma immune evasion. J Exp Med 217:e20191115
Duan Y, Haybaeck J, Yang Z (2020) Therapeutic Potential of PI3K/AKT/mTOR pathway in gastrointestinal stromal tumors: rationale and progress. Cancers (Basel) 12:2972
Elsharkasy OM, Nordin JZ, Hagey DW, de Jong OG, Schiffelers RM, Andaloussi SE, Vader P (2020) Extracellular vesicles as drug delivery systems: Why and how? Adv Drug Deliv Rev 159:332–343
Fearnhead HO, Vandenabeele P, Vanden Berghe T (2017) How do we fit ferroptosis in the family of regulated cell death? Cell Death Differ 24:1991–1998
Federman N (2022) Molecular pathogenesis of desmoid tumor and the role of γ-secretase inhibition. NPJ Precis Oncol 6:62
Filley AC, Henriquez M, Dey M (2017) Recurrent glioma clinical trial, CheckMate-143: the game is not over yet. Oncotarget 8:91779–91794
Gajos-Michniewicz A, Czyz M (2020) WNT signaling in Melanoma. Int J Mol Sci 21:4852
Gao XF, He HQ, Zhu XB, Xie SL, Cao Y (2019) LncRNA SNHG20 promotes tumorigenesis and cancer stemness in glioblastoma via activating PI3K/Akt/mTOR signaling pathway. Neoplasma 66:532–542
Gao XY, Zang J, Zheng MH, Zhang YF, Yue KY, Cao XL, Cao Y, Li XX, Han H, Jiang XF, Liang L (2021) Temozolomide Treatment Induces HMGB1 to Promote the Formation of Glioma Stem Cells via the TLR2/NEAT1/Wnt Pathway in Glioblastoma. Front Cell Dev Biol 9:620883
Ghiaseddin AP, Shin D, Melnick K, Tran DD (2020) Tumor Treating Fields in the Management of Patients with Malignant Gliomas. Curr Treat Options Oncol 21:76
Goker Bagca B, Ozates NP, Biray Avci C (2022) Ruxolitinib enhances cytotoxic and apoptotic effects of temozolomide on glioblastoma cells by regulating WNT signaling pathway-related genes. Med Oncol 40:37
Gong X, Liao X, Huang M (2019) LncRNA CASC7 inhibits the progression of glioma via regulating Wnt/β-catenin signaling pathway. Pathol Res Pract 215:564–570
Guo LP, Zhang ZJ, Li RT, Li HY, Cui YQ (2019) Influences of LncRNA SNHG20 on proliferation and apoptosis of glioma cells through regulating the PTEN/PI3K/AKT signaling pathway. Eur Rev Med Pharmacol Sci 23:253–261
Guo A, Fang G, Lin Z, Zheng S, Zhuang Z, Lin R, Lin Y (2022) Overexpression of lncRNA IRAIN restrains the progression and Temozolomide resistance of glioma via repressing IGF-1R-PI3K-NF-κB signaling pathway. Histol Histopathol 37:543–554
Guttman M, Rinn JL (2012) Modular regulatory principles of large non-coding RNAs. Nature 482:339–346
Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–227
Han Y, Zhou L, Wu T, Huang Y, Cheng Z, Li X, Sun T, Zhou Y, Du Z (2016) Downregulation of lncRNA-MALAT1 Affects Proliferation and the Expression of Stemness Markers in Glioma Stem Cell Line SHG139S. Cell Mol Neurobiol 36:1097–1107
Han N, Yang L, Zhang X, Zhou Y, Chen R, Yu Y, Dong Z, Zhang M (2019) LncRNA MATN1-AS1 prevents glioblastoma cell from proliferation and invasion via RELA regulation and MAPK signaling pathway. Ann Transl Med 7:784
Han M, Wang S, Fritah S, Wang X, Zhou W, Yang N, Ni S, Huang B, Chen A, Li G, Miletic H, Thorsen F, Bjerkvig R, Li X, Wang J (2020) Interfering with long non-coding RNA MIR22HG processing inhibits glioblastoma progression through suppression of Wnt/β-catenin signalling. Brain 143:512–530
Hao C, Chen G, Zhao H, Li Y, Chen J, Zhang H, Li S, Zhao Y, Chen F, Li W, Jiang WG (2020) PD-L1 Expression in Glioblastoma, the Clinical and Prognostic Significance: A Systematic Literature Review and Meta-Analysis. Front Oncol 10:1015
He X, Sheng J, Yu W, Wang K, Zhu S, Liu Q (2021) LncRNA MIR155HG Promotes Temozolomide Resistance by Activating the Wnt/β-Catenin Pathway Via Binding to PTBP1 in Glioma. Cell Mol Neurobiol 41:1271–1284
Herman AB, Tsitsipatis D, Gorospe M (2022) Integrated lncRNA function upon genomic and epigenomic regulation. Mol Cell 82:2252–2266
Hessels D, Klein Gunnewiek JM, van Oort I, Karthaus HF, van Leenders GJ, van Balken B, Kiemeney LA, Witjes JA, Schalken JA (2003) DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol 44:8–15
Hoxhaj G, Manning BD (2020) The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism. Nat Rev Cancer 20:74–88
Huang H, Weng H, Chen J (2020) m(6)A Modification in Coding and Non-coding RNAs: Roles and Therapeutic Implications in Cancer. Cancer Cell 37:270–288
Jackson CM, Choi J, Lim M (2019) Mechanisms of immunotherapy resistance: lessons from glioblastoma. Nat Immunol 20:1100–1109
Ji J, Xu R, Ding K, Bao G, Zhang X, Huang B, Wang X, Martinez A, Wang X, Li G, Miletic H, Thorsen F, Bjerkvig R, Xiang L, Han B, Chen A, Li X, Wang J (2019) Long Noncoding RNA SChLAP1 Forms a Growth-Promoting Complex with HNRNPL in Human Glioblastoma through Stabilization of ACTN4 and Activation of NF-κB Signaling. Clin Cancer Res 25:6868–6881
Jia H, Yan X (2022) lncRNA MEG3 Inhibits the Proliferation and Growth of Glioma Cells by Downregulating Bcl-xL in the PI3K/Akt/NF-kappaB Signal Pathway. Biomed Res Int 2022:3729069
Jin D, Guo J, Wu Y, Du J, Yang L, Wang X, Di W, Hu B, An J, Kong L, Pan L, Su G (2019) m(6)A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis. J Hematol Oncol 12:135
Kannan S, Murugan AK, Balasubramanian S, Munirajan AK, Alzahrani AS (2022) Gliomas: Genetic alterations, mechanisms of metastasis, recurrence, drug resistance, and recent trends in molecular therapeutic options. Biochem Pharmacol 201:115090
Khasraw M, Fujita Y, Lee-Chang C, Balyasnikova IV, Najem H, Heimberger AB (2022) New Approaches to Glioblastoma. Annu Rev Med 73:279–292
Kim SS, Harford JB, Moghe M, Rait A, Pirollo KF, Chang EH (2018) Targeted nanocomplex carrying siRNA against MALAT1 sensitizes glioblastoma to temozolomide. Nucleic Acids Res 46:1424–1440
Lapointe S, Perry A, Butowski NA (2018) Primary brain tumours in adults. Lancet 392:432–446
Levati L, Pagani E, Romani S, Castiglia D, Piccinni E, Covaciu C, Caporaso P, Bondanza S, Antonetti FR, Bonmassar E, Martelli F, Alvino E, D’Atri S (2011) MicroRNA-155 targets the SKI gene in human melanoma cell lines. Pigment Cell Melanoma Res 24:538–550
Lewis MW, Li S, Franco HL (2019) Transcriptional control by enhancers and enhancer RNAs. Transcription 10:171–186
Li J, Zhou L (2018) Overexpression of lncRNA DANCR positively affects progression of glioma via activating Wnt/β-catenin signaling. Biomed Pharmacother 102:602–607
Li D, Ji H, Niu X, Yin L, Wang Y, Gu Y, Wang J, Zhou X, Zhang H, Zhang Q (2020) Tumor-associated macrophages secrete CC-chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer. Cancer Sci 111:47–58
Li C, Feng S, Chen L (2021) MSC-AS1 knockdown inhibits cell growth and temozolomide resistance by regulating miR-373-3p/CPEB4 axis in glioma through PI3K/Akt pathway. Mol Cell Biochem 476:699–713
Liao Y, Shen L, Zhao H, Liu Q, Fu J, Guo Y, Peng R, Cheng L (2017) LncRNA CASC2 Interacts With miR-181a to Modulate Glioma Growth and Resistance to TMZ Through PTEN Pathway. J Cell Biochem 118:1889–1899
Liao Y, Wu X, Wu M, Fang Y, Li J, Tang W (2022) Non-coding RNAs in lung cancer: emerging regulators of angiogenesis. J Transl Med 20:349
Lin L, Cai J, Jiang C (2017) Recent Advances in Targeted Therapy for Glioma. Curr Med Chem 24:1365–1381
Lin C, Wang Y, Dong Y, Lai S, Wang L, Weng S, Zhang X (2022) N6-methyladenosine-mediated SH3BP5-AS1 upregulation promotes GEM chemoresistance in pancreatic cancer by activating the Wnt signaling pathway. Biol Direct 17:33
Liu S, Yang N, Wang L, Wei B, Chen J, Gao Y (2020) lncRNA SNHG11 promotes lung cancer cell proliferation and migration via activation of Wnt/β-catenin signaling pathway. J Cell Physiol 235:7541–7553
Liu SJ, Dang HX, Lim DA, Feng FY, Maher CA (2021a) Long noncoding RNAs in cancer metastasis. Nat Rev Cancer 21:446–460
Liu T, Hu J, Han B, Tan S, Jia W, Xin Y (2021b) A positive feedback loop of lncRNA-RMRP/ZNRF3 axis and Wnt/β-catenin signaling regulates the progression and temozolomide resistance in glioma. Cell Death Dis 12:952
Liu J, Xiao Q, Xiao J, Niu C, Li Y, Zhang X, Zhou Z, Shu G, Yin G (2022) Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal Transduct Target Ther 7:3
Liu F, Xu J, Yang R, Liu S, Hu S, Yan M, Han F (2023) New light on treatment of cervical cancer: Chinese medicine monomers can be effective for cervical cancer by inhibiting the PI3K/Akt signaling pathway. Biomed Pharmacother 157:114084
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW (2021) The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol 23:1231–1251
Lu Y, Tian M, Liu J, Wang K (2021) LINC00511 facilitates Temozolomide resistance of glioblastoma cells via sponging miR-126-5p and activating Wnt/β-catenin signaling. J Biochem Mol Toxicol 35:e22848
Luo J, Manning BD, Cantley LC (2003) Targeting the PI3K-Akt pathway in human cancer: Rationale and promise. Cancer Cell 4:257–262
Luo Y, Huang S, Wei J, Zhou H, Wang W, Yang J, Deng Q, Wang H, Fu Z (2022) Long noncoding RNA LINC01606 protects colon cancer cells from ferroptotic cell death and promotes stemness by SCD1-Wnt/β-catenin-TFE3 feedback loop signalling. Clin Transl Med 12:e752
Lv X, Li Y, Li Y, Li H, Zhou L, Wang B, Zhi Z, Tang W (2019) FAL1: A critical oncogenic long non-coding RNA in human cancers. Life Sci 236:116918
Malakar P, Shilo A, Mogilevsky A, Stein I, Pikarsky E, Nevo Y, Benyamini H, Elgavish S, Zong X, Prasanth KV, Karni R (2017) Long Noncoding RNA MALAT1 Promotes Hepatocellular Carcinoma Development by SRSF1 Upregulation and mTOR Activation. Cancer Res 77:1155–1167
Manning BD, Toker A (2017) AKT/PKB Signaling: Navigating the Network. Cell 169:381–405
Mao C, Wang X, Liu Y, Wang M, Yan B, Jiang Y, Shi Y, Shen Y, Liu X, Lai W, Yang R, Xiao D, Cheng Y, Liu S, Zhou H, Cao Y, Yu W, Muegge K, Yu H, Tao Y (2018) A G3BP1-Interacting lncRNA Promotes Ferroptosis and Apoptosis in Cancer via Nuclear Sequestration of p53. Cancer Res 78:3484–3496
Masuda M, Uno Y, Ohbayashi N, Ohata H, Mimata A, Kukimoto-Niino M, Moriyama H, Kashimoto S, Inoue T, Goto N, Okamoto K, Shirouzu M, Sawa M, Yamada T (2016) TNIK inhibition abrogates colorectal cancer stemness. Nat Commun 7:12586
McKinnon C, Nandhabalan M, Murray SA, Plaha P (2021) Glioblastoma: clinical presentation, diagnosis, and management. BMJ 374:n1560
Molloy NH, Read DE, Gorman AM (2011) Nerve growth factor in cancer cell death and survival. Cancers (basel) 3:510–530
Moser JC, Salvador E, Deniz K, Swanson K, Tuszynski J, Carlson KW, Karanam NK, Patel CB, Story M, Lou E, Hagemann C (2022) The Mechanisms of Action of Tumor Treating Fields. Cancer Res 82:3650–3658
Mou Y, Wang J, Wu J, He D, Zhang C, Duan C, Li B (2019) Ferroptosis, a new form of cell death: opportunities and challenges in cancer. J Hematol Oncol 12:34
Mu M, Niu W, Zhang X, Hu S, Niu C (2020) LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway. Oncogene 39:6879–6892
Napoli S, Munz N, Guidetti F, Bertoni F (2022) Enhancer RNAs (eRNAs) in cancer: the Jacks of all trades. Cancers (Basel) 14:1978
Nayak L, Molinaro AM, Peters K, Clarke JL, Jordan JT, de Groot J, Nghiemphu L, Kaley T, Colman H, McCluskey C, Gaffey S, Smith TR, Cote DJ, Severgnini M, Yearley JH, Zhao Q, Blumenschein WM, Duda DG, Muzikansky A, Jain RK, Wen PY, Reardon DA (2021) Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. Clin Cancer Res 27:1048–1057
Nusse R, Clevers H (2017) Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell 169:985–999
Ouyang J, Zhong Y, Zhang Y, Yang L, Wu P, Hou X, Xiong F, Li X, Zhang S, Gong Z, He Y, Tang Y, Zhang W, Xiang B, Zhou M, Ma J, Li Y, Li G, Zeng Z, Guo C, Xiong W (2022) Long non-coding RNAs are involved in alternative splicing and promote cancer progression. Br J Cancer 126:1113–1124
Panni S, Lovering RC, Porras P, Orchard S (2020) Non-coding RNA regulatory networks. Biochim Biophys Acta Gene Regul Mech 1863:194417
Patil DP, Chen CK, Pickering BF, Chow A, Jackson C, Guttman M, Jaffrey SR (2016) m(6)A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537:369–373
Peng Y (2021) Non-coding RNAs in human cancer. Semin Cancer Biol 75:1–2
Polewski MD, Reveron-Thornton RF, Cherryholmes GA, Marinov GK, Cassady K, Aboody KS (2016) Increased Expression of System xc- in Glioblastoma Confers an Altered Metabolic State and Temozolomide Resistance. Mol Cancer Res 14:1229–1242
Quinn JJ, Chang HY (2016) Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet 17:47–62
Rim EY, Clevers H, Nusse R (2022) The Wnt Pathway: From Signaling Mechanisms to Synthetic Modulators. Annu Rev Biochem 91:571–598
Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166
Sasame J, Ikegaya N, Kawazu M, Natsumeda M, Hayashi T, Isoda M, Satomi K, Tomiyama A, Oshima A, Honma H, Miyake Y, Takabayashi K, Nakamura T, Ueno T, Matsushita Y, Iwashita H, Kanemaru Y, Murata H, Ryo A, Terashima K, Yamanaka S, Fujii Y, Mano H, Komori T, Ichimura K, Cahill DP, Wakimoto H, Yamamoto T, Tateishi K (2022) HSP90 Inhibition Overcomes Resistance to Molecular Targeted Therapy in BRAFV600E-mutant High-grade Glioma. Clin Cancer Res 28:2425–2439
Seoane J, Gomis RR (2017) TGF-β family signaling in tumor suppression and cancer progression. Cold Spring Harb Perspect Biol 9:a022277
Shahcheraghi SH, Tchokonte-Nana V, Lotfi M, Lotfi M, Ghorbani A, Sadeghnia HR (2020) Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review. Curr Pharm Des 26:1729–1741
Sharifzad F, Ghavami S, Verdi J, Mardpour S, Mollapour Sisakht M, Azizi Z, Taghikhani A, Łos MJ, Fakharian E, Ebrahimi M, Hamidieh AA (2019) Glioblastoma cancer stem cell biology: Potential theranostic targets. Drug Resist Updat 42:35–45
Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A (2017) Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell 168:707–723
Sheng J, He X, Yu W, Chen Y, Long Y, Wang K, Zhu S, Liu Q (2021) p53-targeted lncRNA ST7-AS1 acts as a tumour suppressor by interacting with PTBP1 to suppress the Wnt/β-catenin signalling pathway in glioma. Cancer Lett 503:54–68
Shuman S (2020) Transcriptional interference at tandem lncRNA and protein-coding genes: an emerging theme in regulation of cellular nutrient homeostasis. Nucleic Acids Res 48:8243–8254
Siebel C, Lendahl U (2017) Notch Signaling in Development, Tissue Homeostasis, and Disease. Physiol Rev 97:1235–1294
Slack FJ, Chinnaiyan AM (2019) The Role of Non-coding RNAs in Oncology. Cell 179:1033–1055
Spranger S, Bao R, Gajewski TF (2015) Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature 523:231–235
St Laurent G, Wahlestedt C, Kapranov P (2015) The Landscape of long noncoding RNA classification. Trends Genet 31:239–251
Suva ML, Tirosh I (2020) The Glioma Stem Cell Model in the Era of Single-Cell Genomics. Cancer Cell 37:630–636
Svoronos AA, Engelman DM, Slack FJ (2016) OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer. Cancer Res 76:3666–3670
Tan SK, Pastori C, Penas C, Komotar RJ, Ivan ME, Wahlestedt C, Ayad NG (2018) Serum long noncoding RNA HOTAIR as a novel diagnostic and prognostic biomarker in glioblastoma multiforme. Mol Cancer 17:74
Tang F, Wang H, Chen E, Bian E, Xu Y, Ji X, Yang Z, Hua X, Zhang Y, Zhao B (2019) LncRNA-ATB promotes TGF-β-induced glioma cells invasion through NF-κB and P38/MAPK pathway. J Cell Physiol 234:23302–23314
Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, Chen L, Pardoll DM, Topalian SL, Anders RA (2014) Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res 20:5064–5074
Tomar MS, Kumar A, Srivastava C, Shrivastava A (2021) Elucidating the mechanisms of Temozolomide resistance in gliomas and the strategies to overcome the resistance. Biochim Biophys Acta Rev Cancer 1876:188616
Touat M, Idbaih A, Sanson M, Ligon KL (2017) Glioblastoma targeted therapy: updated approaches from recent biological insights. Ann Oncol 28:1457–1472
Tu Z, Li J, Long X, Wu L, Zhu X, Huang K (2022) Transcriptional Patterns of Lower-Grade Glioma Patients with Distinct Ferroptosis Levels, Immunotherapy Response, and Temozolomide Sensitivity. Oxid Med Cell Longev 2022:9408886
Voloshanenko O, Erdmann G, Dubash TD, Augustin I, Metzig M, Moffa G, Hundsrucker C, Kerr G, Sandmann T, Anchang B, Demir K, Boehm C, Leible S, Ball CR, Glimm H, Spang R, Boutros M (2013) Wnt secretion is required to maintain high levels of Wnt activity in colon cancer cells. Nat Commun 4:2610
Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43:904–914
Wang Y, Wang Y, Li J, Zhang Y, Yin H, Han B (2015) CRNDE, a long-noncoding RNA, promotes glioma cell growth and invasion through mTOR signaling. Cancer Lett 367:122–128
Wang X, Lu X, Geng Z, Yang G, Shi Y (2017) LncRNA PTCSC3/miR-574-5p Governs Cell Proliferation and Migration of Papillary Thyroid Carcinoma via Wnt/β-Catenin Signaling. J Cell Biochem 118:4745–4752
Wang X, Yan Y, Zhang C, Wei W, Ai X, Pang Y, Bian Y (2018) Upregulation of lncRNA PlncRNA-1 indicates the poor prognosis and promotes glioma progression by activation of Notch signal pathway. Biomed Pharmacother 103:216–221
Wang X, Hua J, Li J, Zhang J, Dzakah EE, Cao G, Lin W (2022a) Mechanisms of non-coding RNA-modulated alternative splicing in cancer. RNA Biol 19:541–547
Wang Y, Cheng Y, Yang Q, Kuang L, Liu G (2022b) Overexpression of FOXD2-AS1 enhances proliferation and impairs differentiation of glioma stem cells by activating the NOTCH pathway via TAF-1. J Cell Mol Med 26:2620–2632
Wen H, Li Z, Song S, Xu L, Tong X, Yan H (2021) Silencing of lncRNA LBX2-AS1 suppresses glioma cell proliferation and metastasis through the Akt/GSK3β pathway in vitro. Acta Biochim Biophys Sin (shanghai) 53:446–453
Wender RC, Brawley OW, Fedewa SA, Gansler T, Smith RA (2019) A blueprint for cancer screening and early detection: Advancing screening’s contribution to cancer control. CA Cancer J Clin 69:50–79
Wesseling P, Capper D (2018) WHO 2016 Classification of gliomas. Neuropathol Appl Neurobiol 44:139–150
Wu AC, Yang WB, Chang KY, Lee JS, Liou JP, Su RY, Cheng SM, Hwang DY, Kikkawa U, Hsu TI, Wang CY, Chang WC, Chen PY, Chuang JY (2022) HDAC6 involves in regulating the lncRNA-microRNA-mRNA network to promote the proliferation of glioblastoma cells. J Exp Clin Cancer Res 41:47
Xia S, Ji R, Zhan W (2017) Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) inhibits proliferation and invasion of glioma cells by suppressing the Wnt/β-catenin signaling pathway. BMC Neurol 17:30
Xiong Z, Wang L, Wang Q, Yuan Y (2018) LncRNA MALAT1/miR-129 axis promotes glioma tumorigenesis by targeting SOX2. J Cell Mol Med 22:3929–3940
Xu X, Wang Z, Liu N, Cheng Y, Jin W, Zhang P, Wang X, Yang H, Liu H, Zhang Y, Tu Y (2018) Association between SOX9 and CA9 in glioma, and its effects on chemosensitivity to TMZ. Int J Oncol 53:189–202
Xu S, Luo C, Chen D, Tang L, Chen L, Liu Z (2022) Whole transcriptome and proteome analyses identify potential targets and mechanisms underlying tumor treating fields against glioblastoma. Cell Death Dis 13:721
Xue C, Li G, Lu J, Li L (2021) Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression. Signal Transduct Target Ther 6:400
Xue C, Li G, Zheng Q, Gu X, Bao Z, Lu J, Li L (2022) The functional roles of the circRNA/Wnt axis in cancer. Mol Cancer 21:108
Yang XZ, Cheng TT, He QJ, Lei ZY, Chi J, Tang Z, Liao QX, Zhang H, Zeng LS, Cui SZ (2018) LINC01133 as ceRNA inhibits gastric cancer progression by sponging miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway. Mol Cancer 17:126
Yang K, Wu Z, Zhang H, Zhang N, Wu W, Wang Z, Dai Z, Zhang X, Zhang L, Peng Y, Ye W, Zeng W, Liu Z, Cheng Q (2022) Glioma targeted therapy: insight into future of molecular approaches. Mol Cancer 21:39
Yao RW, Wang Y, Chen LL (2019) Cellular functions of long noncoding RNAs. Nat Cell Biol 21:542–551
Yasaswi PS, Shetty K, Yadav KS (2021) Temozolomide nano enabled medicine: promises made by the nanocarriers in glioblastoma therapy. J Control Release 336:549–571
Ye Z, Liu W, Zhuo Q, Hu Q, Liu M, Sun Q, Zhang Z, Fan G, Xu W, Ji S, Yu X, Qin Y, Xu X (2020) Ferroptosis: Final destination for cancer? Cell Prolif 53:e12761
Yu Y, Zhang W, Li A, Chen Y, Ou Q, He Z, Zhang Y, Liu R, Yao H, Song E (2020) Association of Long Noncoding RNA Biomarkers With Clinical Immune Subtype and Prediction of Immunotherapy Response in Patients With Cancer. JAMA Netw Open 3:e202149
Yu L, Wei J, Liu P (2022) Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer. Semin Cancer Biol 85:69–94
Yun D, Wang X, Wang W, Ren X, Li J, Wang X, Liang J, Liu J, Fan J, Ren X, Zhang H, Shang G, Sun J, Chen L, Li T, Zhang C, Yu S, Yang X (2022) A Novel Prognostic Signature Based on Glioma Essential Ferroptosis-Related Genes Predicts Clinical Outcomes and Indicates Treatment in Glioma. Front Oncol 12:897702
Zhan T, Rindtorff N, Boutros M (2017) Wnt signaling in cancer. Oncogene 36:1461–1473
Zhang Y, Wang X (2020) Targeting the Wnt/beta-catenin signaling pathway in cancer. J Hematol Oncol 13:165
Zhang H, Wei DL, Wan L, Yan SF, Sun YH (2017) Highly expressed lncRNA CCND2-AS1 promotes glioma cell proliferation through Wnt/β-catenin signaling. Biochem Biophys Res Commun 482:1219–1225
Zhang M, Weng W, Zhang Q, Wu Y, Ni S, Tan C, Xu M, Sun H, Liu C, Wei P, Du X (2018) The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5. J Hematol Oncol 11:113
Zhang J, Chen G, Gao Y, Liang H (2020) HOTAIR/miR-125 axis-mediated Hexokinase 2 expression promotes chemoresistance in human glioblastoma. J Cell Mol Med 24:5707–5717
Zhao HF, Wang J, Shao W, Wu CP, Chen ZP, To ST, Li WP (2017) Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development. Mol Cancer 16:100
Zhao R, Li B, Zhang S, He Z, Pan Z, Guo Q, Qiu W, Qi Y, Zhao S, Wang S, Chen Z, Zhang P, Guo X, Xue H, Li G (2021) The N(6)-Methyladenosine-Modified Pseudogene HSPA7 Correlates With the Tumor Microenvironment and Predicts the Response to Immune Checkpoint Therapy in Glioblastoma. Front Immunol 12:653711
Zhen Y, Kang C, Xueyan W, Hongzhan L (2020) Research progress of long non-coding RNA in Temozolomide resistant glioma. J Med Postgrad 33:990–994
Zheng Y, Lu S, Xu Y, Zheng J (2019) Long non-coding RNA AGAP2-AS1 promotes the proliferation of glioma cells by sponging miR-15a/b-5p to upregulate the expression of HDGF and activating Wnt/β-catenin signaling pathway. Int J Biol Macromol 128:521–530
Zhong Z, Virshup DM (2020) Wnt Signaling and Drug Resistance in Cancer. Mol Pharmacol 97:72–89
Zhou J, Hu T, Chen Y, Lei D, Chen Q (2019) Expression of lncRNA NEAT1 in human glioma and its relationship with prognosis. Chin J Clin Neurosurg 24:148–150
Zhou XY, Liu H, Ding ZB, Xi HP, Wang GW (2020) lncRNA SNHG16 promotes glioma tumorigenicity through miR-373/EGFR axis by activating PI3K/AKT pathway. Genomics 112:1021–1029
Zhou C, Zhao H, Wang S, Dong C, Yang F, Zhang J (2022a) LncRNA ADAMTS9-AS1 knockdown suppresses cell proliferation and migration in glioma through downregulating Wnt/β-catenin signaling pathway. Bosn J Basic Med Sci 22:395–402
Zhou Q, Liu ZZ, Wu H, Kuang WL (2022c) LncRNA H19 Promotes Cell Proliferation, Migration, and Angiogenesis of Glioma by Regulating Wnt5a/β-Catenin Pathway via Targeting miR-342. Cell Mol Neurobiol 42:1065–1077
Zhou J, Xu N, Liu B, Wang C, He Z, Lenahan C, Tang W, Zeng H, Guo H (2022b) lncRNA XLOC013218 promotes cell proliferation and TMZ resistance by targeting the PIK3R2-mediated PI3K/AKT pathway in glioma. Cancer Sci 113:2681–2692
Zhu J, Tang C, Cong Z, Yuan F, Cai X, Yang J, Ma C (2021) ACT001 reverses resistance of prolactinomas via AMPK-mediated EGR1 and mTOR pathways. Endocr Relat Cancer 29:33–46
Zhu X, Chen D, Sun Y, Yang S, Wang W, Liu B, Gao P, Li X, Wu L, Ma S, Lin W, Ma J, Yan D (2023) LncRNA WEE2-AS1 is a diagnostic biomarker that predicts poor prognoses in patients with glioma. BMC Cancer 23:120
Funding
Natural Science Foundation of Shandong Province, Grant/Award Number: ZR2022MH140; Project funded by China Postdoctoral Science Foundation, Grant/Award Number: 2022M711324.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. JS had the idea for the article. YL, JL, XQ and HL performed the literature search. JS, YL, and FJ revised the work. The first draft of the manuscript was written by HL and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding authors
Ethics declarations
Conflict of Interest
The authors declare no conflicts of interest.
Ethical Approval
Not applicable. There is not any patient in this review.
Consent for Publication
All the authors give consent.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Li, H., Liu, J., Qin, X. et al. Function of Long Noncoding RNAs in Glioma Progression and Treatment Based on the Wnt/β-Catenin and PI3K/AKT Signaling Pathways. Cell Mol Neurobiol 43, 3929–3942 (2023). https://doi.org/10.1007/s10571-023-01414-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-023-01414-9