Abstract
Introduction
Colorectal cancer (CRC) is the third most prevalent cancer and the second significant cause of cancer-associated death worldwide. The microRNA-30 is a substantial member of the miRNA family and plays a vital role in expanding several cancers. This microRNA potentially targets interleukin 6 as an inflammatory cytokine in CRC.
Materials and methods
MSCs were isolated and identified from mice bone marrow and then transduced with lentiviruses containing miR-30C. Transfected MSCs were collected to evaluate IL-6 levels, CT-26 cells were also co-cultured with MSCs, and the effect of apoptosis and IL-6 on the supernatant was assessed.
Results
Our result showed the expression of IL-6 mRNA and the level of protein were decreased in the supernatant of miR-30-transduced MSC cells compared to the control group. In addition, the rate of apoptosis was assessed, and the obtained data revealed the induction of apoptosis in CT-26 cells when they are in the vicinity of miR-30c-transduced MSCs.
Discussion and conclusion
We demonstrated that downregulation of miR-30c was significantly correlated with CRC progression and survival. So, the present study elucidated the anticancer effects of miR-30c in CRC and presented a novel target for CRC therapy.
Similar content being viewed by others
References
Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F (2017) Global patterns and trends in colorectal cancer incidence and mortality. Gut 66(4):683–691
Barez SR, Attar AM, Aghaei M (2021) MicroRNA-30c-2-3p regulates ER stress and induces apoptosis in ovarian cancer cells underlying ER stress. EXCLI J 20:922
Bockhorn J, Yee K, Chang Y-F, Prat A, Huo D, Nwachukwu C et al (2013a) MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion. Breast Cancer Res Treat 137(2):373–382
Bockhorn J, Dalton R, Nwachukwu C, Huang S, Prat A, Yee K et al (2013b) MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. Nat Commun 4(1):1–14
Bracken CP, Scott HS, Goodall GJ (2016) A network-biology perspective of microRNA function and dysfunction in cancer. Nat Rev Genet 17(12):719
Brennecke J, Stark A, Russell RB, Cohen SM (2005) Principles of microRNA–target recognition. PLoS Biol 3(3):e85
Chung YC, Chang YF (2003) Serum interleukin-6 levels reflect the disease status of colorectal cancer. J Surg Oncol 83(4):222–226
Cuiffo BG, Karnoub AE (2012) Mesenchymal stem cells in tumor development: emerging roles and concepts. Cell Adh Migr 6(3):220–230
Derakhshani A, Kamyar KF, Barzegari Banadkoki S, Shirazi FH, Barati M, Fereidouni M et al (2019) Optimization of induction parameters, structure quality assessment by ATR-FTIR and in silico characterization of expressed recombinant polcalcin in three different strains of Escherichia coli. Int J Biol Macromol 138:97–105
Duecker RP, De Mir MI, Jerkic SP, Kochems A, Gottwald G, Moreno-Galdó A et al (2022) Epigenetic regulation of inflammation by microRNAs in post-infectious bronchiolitis obliterans. Clin Transl Immunol 11(2):e1376
Han W, Cui H, Liang J, Su X (2020) Role of MicroRNA-30c in cancer progression. J Cancer 11(9):2593
Hartman ZC, Poage GM, Den Hollander P, Tsimelzon A, Hill J, Panupinthu N et al (2013) Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8. Can Res 73(11):3470–3480
Jones SA, Jenkins BJ (2018) Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat Rev Immunol 18(12):773–789
Komoda H, Tanaka Y, Honda M, Matsuo Y, Hazama K, Takao T (1998) Interleukin-6 levels in colorectal cancer tissues. World J Surg 22(8):895–898
Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, Oreshkova T, Belemezova K et al (2014) Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells 6(5):552
Lazennec G, Lam PY (2016) Recent discoveries concerning the tumor-mesenchymal stem cell interactions. Biochimica Et Biophysica Acta (BBA) 1866(2):290–299
Lee HY, Hong IS (2017) Double-edged sword of mesenchymal stem cells: cancer-promoting versus therapeutic potential. Cancer Sci 108(10):1939–1946
Li L, Han R, Xiao H, Lin C, Wang Y, Liu H et al (2014) Metformin sensitizes EGFR-TKI–resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal. Clin Cancer Res 20(10):2714–2726
Li P, Zhong X, Li J, Liu H, Ma X, He R et al (2018) MicroRNA-30c-5p inhibits NLRP3 inflammasome-mediated endothelial cell pyroptosis through FOXO3 down-regulation in atherosclerosis. Biochem Biophys Res Commun 503(4):2833–2840
Lippitz BE, Harris RA (2016) Cytokine patterns in cancer patients: a review of the correlation between interleukin 6 and prognosis. Oncoimmunology 5(5):e1093722
Ma T, Zhao Y, Lu Q, Lu Y, Liu Z, Xue T et al (2018) MicroRNA-30c functions as a tumor suppressor via targeting SNAI1 in esophageal squamous cell carcinoma. Biomed Pharmacother 98:680–686
Mahjoor M, Afkhami H, Mollaei M, Nasr A, Shahriary S, Khorrami S (2021a) MicroRNA-30c delivered by bone marrow-mesenchymal stem cells induced apoptosis and diminished cell invasion in U-251 glioblastoma cell line. Life Sci 279:119643
Mahjoor M, Afkhami H, Mollaei M, Nasr A, Shahriary S, Khorrami S (2021b) MicroRNA-30c delivered by bone marrow-mesenchymal stem cells induced apoptosis and diminished cell invasion in U-251 glioblastoma cell line. Life Sci 279:119643
Mano Y, Aishima S, Fujita N, Tanaka Y, Kubo Y, Motomura T et al (2013) Tumor-associated macrophage promotes tumor progression via STAT3 signaling in hepatocellular carcinoma. Pathobiology 80(3):146–154
Mao L, Liu S, Hu L, Jia L, Wang H, Guo M et al (2018) miR-30 family: a promising regulator in development and disease. BioMed Res Int 2018:1–8
Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi MJ (2017) Colorectal carcinoma: a general overview and future perspectives in colorectal cancer. Int J Mol Sci 18(1):197
McCann JV, Xiao L, Kim DJ, Khan OF, Kowalski PS, Anderson DG et al (2019) Endothelial miR-30c suppresses tumor growth via inhibition of TGF-β–induced Serpine1. J Clin Invest 129(4):1654–1670
Mi F, Gong L (2017) Secretion of interleukin-6 by bone marrow mesenchymal stem cells promotes metastasis in hepatocellular carcinoma. Biosci Rep. https://doi.org/10.1042/BSR20170181
Moslemi M, Sohrabi E, Azadi N, Zekri A, Afkhami H, Khaledi M et al (2020) Expression analysis of EEPD1 and MUS81 genes in breast Cancer. Bio J Sci Tech Res 29:22556–22564
Moslemi M, Moradi Y, Dehghanbanadaki H, Afkhami H, Khaledi M, Sedighimehr N et al (2021) The association between ATM variants and risk of breast cancer: a systematic review and meta-analysis. BMC Cancer 21(1):1–12
Ridge SM, Sullivan FJ, Glynn SA (2017) Mesenchymal stem cells: key players in cancer progression. Mol Cancer 16(1):31
Shah MY, Ferrajoli A, Sood AK, Lopez-Berestein G, Calin GA (2016) microRNA therapeutics in cancer—an emerging concept. EBioMedicine 12:34–42
Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RG, Barzi A et al (2017) Colorectal cancer statistics, 2017. CA: A Cancer J Clinicians 67(3):177–193
Sohrabi E, Moslemi M, Rezaie E, Nafissi N, Khaledi M, Afkhami H et al (2021) The tissue expression of MCT3, MCT8, and MCT9 genes in women with breast cancer. Genes Genomics 43(9):1065–1077
Spinelli SV, Fernández RDV, Zoff L, Bongiovanni B, Díaz A, D’Attilio L et al (2017) miR-30c is specifically repressed in patients with active pulmonary tuberculosis. Tuberculosis 105:73–79
Sun R, Muheremu A, Hu Y (2018) miRNA-30c can be used as a target in the diagnosis and treatment of osteosarcoma. Onco Targets Ther 11:9091
Ullah I, Subbarao RB, Rho GJ (2015) Human mesenchymalstem cells—current trends and future prospective 35(2):e00191
Unver N, McAllister F (2018) IL-6 family cytokines: key inflammatory mediators as biomarkers and potential therapeutic targets. Cytokine Growth Factor Rev 41:10–17
Wang Z, Si X, Xu A, Meng X, Gao S, Qi Y et al (2013) Activation of STAT3 in human gastric cancer cells via interleukin (IL)-6-type cytokine signaling correlates with clinical implications. PLoS ONE 8(10):e75788
Wang Y, Pei X, Xu P, Tan Z, Zhu Z, Zhang G et al (2020) E2F7, regulated by miR-30c, inhibits apoptosis and promotes cell cycle of prostate cancer cells. Oncol Rep 44(3):849–862
Wolfe AR, Trenton NJ, Debeb BG, Larson R, Ruffell B, Chu K et al (2016) Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models. Oncotarget 7(50):82482
Xia Y, Chen Q, Zhong Z, Xu C, Wu C, Liu B et al (2013) Down-regulation of miR-30c promotes the invasion of non-small cell lung cancer by targeting MTA1. Cell Physiol Biochem 32(2):476–485
Zeng J, Tang Z-H, Liu S, Guo S-S (2017) Clinicopathological significance of overexpression of interleukin-6 in colorectal cancer. World J Gastroenterol 23(10):1780
Zhang Q, Yu L, Qin D, Huang R, Jiang X, Zou C et al (2015) Role of microRNA-30c targeting ADAM19 in colorectal cancer. PLoS ONE 10(3):e0120698
Zhang X, Hu F, Li G, Li G, Yang X, Liu L et al (2018) Human colorectal cancer-derived mesenchymal stem cells promote colorectal cancer progression through IL-6/JAK2/STAT3 signaling. Cell Death Dis 9(2):1–13
Zhao Q, Ren H, Han Z (2016) Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases. J Cell Immunother 2(1):3–20
Zhou H, Xu X, Xun Q, Yu D, Ling J, Guo F et al (2012) microRNA-30c negatively regulates endometrial cancer cells by targeting metastasis-associated gene-1. Oncol Rep 27(3):807–812
Zhou Z, Chen Y, Zhang D, Wu S, Liu T, Cai G et al (2019) MicroRNA-30–3p suppresses inflammatory factor-induced endothelial cell injury by targeting TCF21. Mediators Inflammation 2019:1–14
Funding
There is no funding sources.
Author information
Authors and Affiliations
Contributions
MM: data collection; HA: data collection; MN: writing manuscript; AN: help to mn for writing manuscript; SK: corresponding author.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there is no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Mahjoor, M., Afkhami, H., Najafi, M. et al. The role of microRNA-30c in targeting interleukin 6, as an inflammatory cytokine, in the mesenchymal stem cell: a therapeutic approach in colorectal cancer. J Cancer Res Clin Oncol 149, 3149–3160 (2023). https://doi.org/10.1007/s00432-022-04123-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-022-04123-w