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Recent Patents on Anti-Cancer Drug Discovery

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ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

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Research Article

MiR-125b Inhibits Cell Proliferation and Induces Apoptosis in Human Colon Cancer SW480 Cells via Targeting STAT3

Author(s): Junhe Zhang*, Wenwen Yang, Yunxi Xiao and Linlin Shan

Volume 17, Issue 2, 2022

Published on: 08 July, 2021

Page: [187 - 194] Pages: 8

DOI: 10.2174/1574892816666210708165037

Price: $65

Abstract

Background: Colon cancer is one of the most common types of cancer worldwide. Multiple studies have unveiled the key role of microRNAs (miRNAs) in the development of various types of cancer. However, the mechanism of action of miR-125b in the development and progression of colon cancer remains unknown.

Objectives: In this study, we explored the association of miR-125b and signal transducer and activator of transcription 3 (STAT3) and its role in the proliferation and apoptosis of SW480 colon cancer cells.

Methods: The miR-125b expression in NCM460, SW480, HT29, and HCT8 cells was detected using quantitative real-time polymerase chain reaction (qRT-PCR). SW480 cells were transfected with lentiviruses of GFP-miR-125b and GFP-NC to establish a stable miR-125b overexpression colon cancer cell model and a control model. The targeting relationship between miR-125b and STAT3 was analyzed using bioinformatics and verified by the dual-luciferase reporter gene assay. Cell proliferation and apoptosis were assessed using the Cell Counting Kit-8 assay and TUNEL staining. The expression levels of STAT3, Bcl-2, and Bax were analyzed using Western blot analysis.

Results: It was found that the relative mRNA expression of miR-125b was decreased in SW480, HT29, and HCT8 cells compared with that in NCM460 cells (P<0.05). The luciferase reporter gene assay confirmed that miR-125b downregulated the STAT3 gene expression (P<0.05). Overexpression of miR-125b inhibited proliferation and promoted apoptosis in SW480 colon cancer cells and was accompanied by upregulated Bax expression and downregulated Bcl-2 expression (P<0.05). Re-expression of STAT3 promoted cell proliferation and inhibited cell apoptosis, whereas Bcl-2 expression increased, and Bax expression decreased (P<0.05).

Conclusion: The miR-125b regulates the expression of Bax and Bcl-2 by downregulating the expression of STAT3, thereby inhibiting proliferation and inducing apoptosis of SW480 colon cancer cells.

Keywords: Apoptosis, Bcl-2, colon cancer, miR-125b, proliferation, STAT3.

« Previous Next »
[1]
Ekine-Afolabi BA, Njan AA, Rotimi SO, et al. The impact of diet on the involvement of non-coding RNAs, extracellular vesicles, and gut microbiome-virome in colorectal cancer initiation and progression. Front Oncol 2020; 10: 583372.
[http://dx.doi.org/10.3389/fonc.2020.583372] [PMID: 33381452]
[2]
Yahagi M, Okabayashi K, Hasegawa H, Tsuruta M, Kitagawa Y. The worse prognosis of right-sided compared with left-sided colon cancers: A systematic review and meta-analysis. J Gastrointest Surg 2016; 20(3): 648-55.
[http://dx.doi.org/10.1007/s11605-015-3026-6] [PMID: 26573851]
[3]
Dayal S. Synchronous colon carcinoma and tuberculosis: Coincidence or linked. Euroasian J Hepatogastroenterol 2017; 7(1): 97-8.
[http://dx.doi.org/10.5005/jp-journals-10018-1224] [PMID: 29201785]
[4]
Lee SH, Bajracharya R, Min JY, Han JW, Park BJ, Han HK. Strategic approaches for colon targeted drug delivery: An overview of recent advancements. Pharmaceutics 2020; 12(1): 68.
[http://dx.doi.org/10.3390/pharmaceutics12010068] [PMID: 31952340]
[5]
Skelton WP IV, Franke AJ, Iqbal A, George TJ. Comprehensive literature review of randomized clinical trials examining novel treatment advances in patients with colon cancer. J Gastrointest Oncol 2020; 11(4): 790-802.
[http://dx.doi.org/10.21037/jgo-20-184] [PMID: 32953161]
[6]
Croce CM. MicroRNA signatures in human ovarian cancer. US2015024963, 2015.
[7]
Calon J, Mlecnik B, Pages F, Fridman H. Method for predicting the outcome of colon cancer by analysing miRNA expression. US2018208995, 2018.
[8]
Wu J, Jiang C. MicroRNA molecular marker for diagnosing glioma and application of microRNA molecular marker. CN104313171, 2015.
[9]
Hrovatin K, Kunej T. Classification of miRNA-related sequence variations. Epigenomics 2018; 10(4): 463-81.
[http://dx.doi.org/10.2217/epi-2017-0126] [PMID: 29569482]
[10]
Yates LA, Norbury CJ, Gilbert RJ. The long and short of microRNA. Cell 2013; 153(3): 516-9.
[http://dx.doi.org/10.1016/j.cell.2013.04.003] [PMID: 23622238]
[11]
Liu W, Hu J, Zhou K, et al. Serum exosomal miR-125b is a novel prognostic marker for hepatocellular carcinoma. OncoTargets Ther 2017; 10: 3843-51.
[http://dx.doi.org/10.2147/OTT.S140062] [PMID: 28814883]
[12]
Zeng JF, Zeng ZL, Zhang K, et al. miR-23b-3p and miR-125b-5p downregulate apo(a) expression by targeting Ets1 in HepG2 cells. Cell Biol Int 2018; 42(3): 313-23.
[http://dx.doi.org/10.1002/cbin.10896] [PMID: 29064597]
[13]
Tong Z, Liu N, Lin L, Guo X, Yang D, Zhang Q. miR-125a-5p inhibits cell proliferation and induces apoptosis in colon cancer via targeting BCL2, BCL2L12 and MCL1. Biomed Pharmacother 2015; 75: 129-36.
[http://dx.doi.org/10.1016/j.biopha.2015.07.036] [PMID: 26297542]
[14]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25(4): 402-8.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[15]
Fan JD, Jiang LX, Zhou ZW. Recombinant lentiviral vector preparation. US2015056696, 2015.
[16]
Zhang JH, Du AL, Wang L, Wang XY, Gao JH, Wang TY. Episomal lentiviral vector-mediated miR-145 overexpression inhibits proliferation and induces apoptosis of human esophageal carcinomas cells. Recent Patents Anticancer Drug Discov 2016; 11(4): 453-60.
[http://dx.doi.org/10.2174/1574892811666160822161157] [PMID: 27549139]
[17]
Zhang JH, Xia HB. Lentiviral-mediated overexpression of microRNA-141 promotes cell proliferation and inhibits apoptosis in human esophageal squamous cell carcinoma. Recent Patents Anticancer Drug Discov 2019; 14(2): 170-6.
[http://dx.doi.org/10.2174/1574892814666181231142136] [PMID: 30599110]
[18]
Zhang J, Chai S, Ruan X. SOX4 serves an oncogenic role in the tumourigenesis of human breast adenocarcinoma by promoting cell proliferation, migration and inhibiting apoptosis. Recent Patents Anticancer Drug Discov 2020; 15(1): 49-58.
[http://dx.doi.org/10.2174/1574892815666200212112119] [PMID: 32048979]
[19]
Chang GJ, You YNY, Russell CA, et al. Young-onset colon cancer and recurrence risk by gene expression. J Natl Cancer Inst 2020; 112(11): 1170-3.
[http://dx.doi.org/10.1093/jnci/djaa019] [PMID: 32040172]
[20]
Wang SS. Application of miR-125b and chemotherapeutic agent in preparation of drug for treating thyroid cancer. CN108721318, 2018.
[21]
Garnis C, Guillaud M. Methods for evaluating head and neck cancers. US2020370125, 2020.
[22]
Li LN, Xiao T, Yi HM, et al. MiR-125b increases nasopharyngeal carcinoma radioresistance by targeting A20/NF-κB signaling pathway. Mol Cancer Ther 2017; 16(10): 2094-106.
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0385] [PMID: 28698199]
[23]
Wang Y, Wei Y, Fan X, et al. MicroRNA-125b as a tumor suppressor by targeting MMP11 in breast cancer. Thorac Cancer 2020; 11(6): 1613-20.
[http://dx.doi.org/10.1111/1759-7714.13441] [PMID: 32291953]
[24]
Renou L, Boelle PY, Deswarte C, et al. Homeobox protein TLX3 activates miR-125b expression to promote T-cell acute lymphoblastic leukemia. Blood Adv 2017; 1(12): 733-47.
[http://dx.doi.org/10.1182/bloodadvances.2017005538] [PMID: 29296717]
[25]
Shi XB, Xue L, Ma AH, Tepper CG, Kung HJ, White RW. miR-125b promotes growth of prostate cancer xenograft tumor through targeting pro-apoptotic genes. Prostate 2011; 71(5): 538-49.
[http://dx.doi.org/10.1002/pros.21270] [PMID: 20886540]
[26]
Li G, So AY, Sookram R, et al. Epigenetic silencing of miR-125b is required for normal B-cell development. Blood 2018; 131(17): 1920-30.
[http://dx.doi.org/10.1182/blood-2018-01-824540] [PMID: 29555645]
[27]
Nie J, Jiang HC, Zhou YC, et al. MiR-125b regulates the proliferation and metastasis of triple negative breast cancer cells via the Wnt/β-catenin pathway and EMT. Biosci Biotechnol Biochem 2019; 83(6): 1062-71.
[http://dx.doi.org/10.1080/09168451.2019.1584521] [PMID: 30950326]
[28]
Zhao X, He W, Li J, et al. MiRNA-125b inhibits proliferation and migration by targeting SphK1 in bladder cancer. Am J Transl Res 2015; 7(11): 2346-54.
[PMID: 26807182]
[29]
González-Arriagada WA, Olivero P, Rodríguez B, Lozano-Burgos C, de Oliveira CE, Coletta RD. Clinicopathological significance of miR-26, miR-107, miR-125b, and miR-203 in head and neck carcinomas. Oral Dis 2018; 24(6): 930-9.
[http://dx.doi.org/10.1111/odi.12872] [PMID: 29667275]
[30]
Aittomäki S, Pesu M. Therapeutic targeting of the Jak/STAT pathway. Basic Clin Pharmacol Toxicol 2014; 114(1): 18-23.
[http://dx.doi.org/10.1111/bcpt.12164] [PMID: 24164900]
[31]
O’Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. The JAK-STAT pathway: Impact on human disease and therapeutic intervention. Annu Rev Med 2015; 66: 311-28.
[http://dx.doi.org/10.1146/annurev-med-051113-024537] [PMID: 25587654]
[32]
Hin Tang JJ, Hao Thng DK, Lim JJ, Toh TB. JAK/STAT signaling in hepatocellular carcinoma. Hepat Oncol 2020; 7(1): HEP18.
[http://dx.doi.org/10.2217/hep-2020-0001] [PMID: 32273976]
[33]
Hillmer EJ, Zhang H, Li HS, Watowich SS. STAT3 signaling in immunity. Cytokine Growth Factor Rev 2016; 31: 1-15.
[http://dx.doi.org/10.1016/j.cytogfr.2016.05.001] [PMID: 27185365]
[34]
Banerjee K, Resat H. Constitutive activation of STAT3 in breast cancer cells: A review. Int J Cancer 2016; 138(11): 2570-8.
[http://dx.doi.org/10.1002/ijc.29923] [PMID: 26559373]
[35]
Hu YS, Han X, Liu XH. STAT3: A Potential Drug Target for Tumor and Inflammation. Curr Top Med Chem 2019; 19(15): 1305-17.
[http://dx.doi.org/10.2174/1568026619666190620145052] [PMID: 31218960]
[36]
Wang M, Yuang-Chi Chang A. Molecular mechanism of action and potential biomarkers of growth inhibition of synergistic combination of afatinib and dasatinib against gefitinib-resistant non-small cell lung cancer cells. Oncotarget 2018; 9(23): 16533-46.
[http://dx.doi.org/10.18632/oncotarget.24814] [PMID: 29662665]
[37]
Yu F, Qiao P, Yin G, et al. RHPN2 promotes malignant cell behaviours in ovarian cancer by activating STAT3 signalling. OncoTargets Ther 2020; 13: 11517-27.
[http://dx.doi.org/10.2147/OTT.S272752] [PMID: 33204106]
[38]
Ma JH, Qin L, Li X. Role of STAT3 signaling pathway in breast cancer. Cell Commun Signal 2020; 18(1): 33.
[http://dx.doi.org/10.1186/s12964-020-0527-z] [PMID: 32111215]
[39]
Srivastava J, DiGiovanni J. Non-canonical Stat3 signaling in cancer. Mol Carcinog 2016; 55(12): 1889-98.
[http://dx.doi.org/10.1002/mc.22438] [PMID: 26649644]
[40]
Wang Y, Shen Y, Wang S, Shen Q, Zhou X. The role of STAT3 in leading the crosstalk between human cancers and the immune system. Cancer Lett 2018; 415: 117-28.
[http://dx.doi.org/10.1016/j.canlet.2017.12.003] [PMID: 29222039]
[41]
Guha P, Gardell J, Darpolor J, et al. STAT3 inhibition induces Bax-dependent apoptosis in liver tumor myeloid-derived suppressor cells. Oncogene 2019; 38(4): 533-48.
[http://dx.doi.org/10.1038/s41388-018-0449-z] [PMID: 30158673]
[42]
Pepper C, Hoy T, Bentley DP. Bcl-2/Bax ratios in chronic lymphocytic leukaemia and their correlation with in vitro apoptosis and clinical resistance. Br J Cancer 1997; 76(7): 935-8.
[http://dx.doi.org/10.1038/bjc.1997.487] [PMID: 9328155]
[43]
Peña-Blanco A, García-Sáez AJ. Bax, Bak and beyond - mitochondrial performance in apoptosis. FEBS J 2018; 285(3): 416-31.
[http://dx.doi.org/10.1111/febs.14186] [PMID: 28755482]
[44]
Kolluri SK, Kopparapu PR, Pearce M. Small molecule bcl-2 functional converters as cancer therapeutics. US2019336469, 2019.
[45]
Walensky LD, Pritz J, Wachter F. Small molecule sensitization of BAX activation for induction of cell death. AU2018236233, 2019.
[46]
Chen W, Shen X, Ma L, et al. Phenolic compounds from polygonum chinense induce growth inhibition and apoptosis of cervical cancer SiHa cells. BioMed Res Int 2020; 2020: 8868508.
[http://dx.doi.org/10.1155/2020/8868508] [PMID: 33381593]
[47]
Wang M, Lu X, Dong X, et al. pERK1/2 silencing sensitizes pancreatic cancer BXPC-3 cell to gemcitabine-induced apoptosis via regulating Bax and Bcl-2 expression. World J Surg Oncol 2015; 13: 66.
[http://dx.doi.org/10.1186/s12957-015-0451-7] [PMID: 25880226]
[48]
Zhou N, Wei ZX, Qi ZX. Inhibition of autophagy triggers melatonin-induced apoptosis in glioblastoma cells. BMC Neurosci 2019; 20(1): 63.
[http://dx.doi.org/10.1186/s12868-019-0545-1] [PMID: 31870319]
[49]
Linjawi A, Kontogiannea M, Halwani F, Edwardes M, Meterissian S. Prognostic significance of p53, bcl-2, and Bax expression in early breast cancer. J Am Coll Surg 2004; 198(1): 83-90.
[http://dx.doi.org/10.1016/j.jamcollsurg.2003.08.008] [PMID: 14698315]
[50]
Kim R, Emi M, Tanabe K, Toge T. Therapeutic potential of antisense Bcl-2 as a chemosensitizer for cancer therapy. Cancer 2004; 101(11): 2491-502.
[http://dx.doi.org/10.1002/cncr.20696] [PMID: 15503311]

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