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Research Article

Downregulation of Serum miR-133b and miR-206 Associate with Clinical Outcomes of Progression as Monitoring Biomarkers for Metastasis Colorectal Cancer Patients

Author(s): Surasak Wanram*, Namphon Klaewkla and Parichart Pinyosri

Volume 13, Issue 1, 2024

Published on: 12 January, 2024

Page: [56 - 62] Pages: 7

DOI: 10.2174/0122115366266024240101075745

open access plus

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer in the world. Noncoding RNAs or microRNAs (miRNAs; miRs) biomarkers can play a role in cancer carcinogenesis and progression. Specific KRAS and EGFR mutation are associated with CRC development playing a role in controlling the cellular process as epigenetic events. Circulating serum miRs can serve for early diagnosis, monitoring, and prognosis of CRC as biomarkers but it is still unclear, clinically.

Objective: To determine potential biomarkers of circulating serum miR-133b and miR-206 in CRC patients

Methods: Bioinformatic prediction of microRNA was screened followed by TargetScanHuman7.2, miRTar2GO, miRDB, MiRanda, and DIANA-microT-CDS. Forty-four CRC serum (19 locally advanced, 23 distant advanced CRC) and 12 normal serum samples were subsequently extracted for RNA isolation, cDNA synthesis, and miR validation. The candidate circulating serum miR-133b and miR-206 were validated resulting in a relative expression via quantitative RT-PCR. Relative expression was normalized to the spike-internal control and compared to normal samples as 1 using the -2ΔΔCt method in principle.

Results: Our results represented 9 miRs of miR-206, miR-155-5p, miR-143-3p, miR-193a-3p, miR-30a- 5p, miR-30d-5p, miR-30e-5p, miR-543, miR-877-5p relate to KRAS-specific miRs, whereas, 9 miRs of miR-133b, miR-302a-3p, miR-302b-3p, miR-302d-3p, miR-302e, miR-520a-3p, miR-520b, miR-520c- 3p and miR-7-5p relevance to EGFR-specific miRs by using the bioinformatic prediction tools. Our results showed a decreased expression level of circulating serum miR-133b as well as miR-206 associating with CRC patients (local and advanced metastasis) when compared to normal (P < 0.05), significantly.

Conclusion: The circulating serum miR-133b and miR-206 can serve as significant biomarkers for monitoring the clinical outcome of progression with metastatic CRC patients. Increased drug-responsive CRC patients associated with crucial molecular intervention should be further explored, clinically.

Keywords: Colorectal cancer, circulating microRNAs, prognostic biomarkers, serum miR-133b, serum miR-206, miRNAs validation.

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[1]
Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin 2023; 73(3): 233-54.
[http://dx.doi.org/10.3322/caac.21772] [PMID: 36856579]
[2]
Hull R, Francies FZ, Oyomno M, Dlamini Z. Colorectal cancer genetics, incidence, and risk factors: In search for targeted therapies. Cancer Manag Res 2020; 12(12): 9869-82.
[http://dx.doi.org/10.2147/CMAR.S251223] [PMID: 33116845]
[3]
Zheng S, Schrijvers JJA, Greuter MJW, Kats-Ugurlu G, Lu W, de Bock GH. Effectiveness of colorectal cancer (CRC) screening on all-cause and CRC-specific mortality reduction: A systematic review and meta-analysis. Cancers (Basel) 2023; 15(7): 1948.
[http://dx.doi.org/10.3390/cancers15071948] [PMID: 37046609]
[4]
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[5]
Xue VW, Wong CSC, Cho WCS. Early detection and monitoring of cancer in liquid biopsy: advances and challenges. Expert Rev Mol Diagn 2019; 19(4): 273-6.
[http://dx.doi.org/10.1080/14737159.2019.1583104] [PMID: 30760042]
[6]
Grady WM, Carethers JM. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology 2008; 135(4): 1079-99.
[http://dx.doi.org/10.1053/j.gastro.2008.07.076] [PMID: 18773902]
[7]
Nguyen LH, Goel A, Chung DC. Pathways of colorectal carcinogenesis. Gastroenterology 2020; 158(2): 291-302.
[http://dx.doi.org/10.1053/j.gastro.2019.08.059] [PMID: 31622622]
[8]
Janani B, Vijayakumar M, Priya K, et al. EGFR-based targeted therapy for colorectal cancer-promises and challenges. Vaccines 2022; 10(4): 499.
[http://dx.doi.org/10.3390/vaccines10040499] [PMID: 35455247]
[9]
Zhu G, Pei L, Xia H, Tang Q, Bi F. Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer. Mol Cancer 2021; 20(1): 143.
[http://dx.doi.org/10.1186/s12943-021-01441-4] [PMID: 34742312]
[10]
Corso G, Pascale V, Flauti G, Marrelli D, Roviello F. Oncogenic mutations in colorectal cancer, indications for anatomical sites, and targeted intervention. J Clin Oncol 2013; 31(15): 22037.
[11]
Ben Brahim E, Ayari I, Jouini R, et al. Expression of epidermal growth factor receptor (EGFR) in colorectal cancer: An immunohistochemical study. Arab J Gastroenterol 2018; 19(3): 121-4.
[http://dx.doi.org/10.1016/j.ajg.2018.08.002] [PMID: 30243897]
[12]
Yarom N, Gresham G, Boame N, Jonker D. KRAS status as a predictor of chemotherapy activity in patients with metastatic colorectal cancer. Clin Colorectal Cancer 2019; 18(4): e309-15.
[http://dx.doi.org/10.1016/j.clcc.2019.05.004] [PMID: 31547963]
[13]
Herreros VM, Duran SS, Martín AC, Pérez PR, Villa NE, Marcuello M, et al. Plasma microRNA signature validation for early detection of colorectal cancer. Clin Transl Gastroenterol 2019; 10(1): 00003.
[14]
Nagy ZB, Barták BK, Kalmár A, et al. Comparison of circulating miRNAs expression alterations in matched tissue and plasma samples during colorectal cancer progression. Pathol Oncol Res 2019; 25(1): 97-105.
[http://dx.doi.org/10.1007/s12253-017-0308-1] [PMID: 28980150]
[15]
Sarvizadeh M, Malekshahi ZV, Razi E, Sharifi H, Moussavi N, Taghizadeh M. MicroRNA: A new player in response to therapy for colorectal cancer. J Cell Physiol 2019; 234(6): 8533-40.
[http://dx.doi.org/10.1002/jcp.27806] [PMID: 30478837]
[16]
Humphreys KJ, McKinnon RA, Michael MZ. miR-18a inhibits CDC42 and plays a tumour suppressor role in colorectal cancer cells. PLoS One 2014; 9(11): e112288.
[http://dx.doi.org/10.1371/journal.pone.0112288] [PMID: 25379703]
[17]
Liu J, Chen Z, Xiang J, Gu X. MicroRNA-155 acts as a tumor suppressor in colorectal cancer by targeting CTHRC1 in�vitro. Oncol Lett 2018; 15(4): 5561-8.
[http://dx.doi.org/10.3892/ol.2018.8069] [PMID: 29556299]
[18]
Ni S, Weng W, Xu M, et al. miR-106b-5p inhibits the invasion and metastasis of colorectal cancer by targeting CTSA. OncoTargets Ther 2018; 11: 3835-45.
[http://dx.doi.org/10.2147/OTT.S172887] [PMID: 30013364]
[19]
Zhang N, Hu X, Du Y, Du J. The role of miRNAs in colorectal cancer progression and chemoradiotherapy. Biomed Pharmacother 2021; 134: 111099.
[http://dx.doi.org/10.1016/j.biopha.2020.111099] [PMID: 33338745]
[20]
Su M, Qin B, Liu F, Chen Y, Zhang R. miR 885 5p upregulation promotes colorectal cancer cell proliferation and migration by targeting suppressor of cytokine signaling. Oncol Lett 2018; 16(1): 65-72.
[http://dx.doi.org/10.3892/ol.2018.8645] [PMID: 29928388]
[21]
Ji D, Chen Z, Li M, et al. MicroRNA-181a promotes tumor growth and liver metastasis in colorectal cancer by targeting the tumor suppressor WIF-1. Mol Cancer 2014; 13(1): 86.
[http://dx.doi.org/10.1186/1476-4598-13-86] [PMID: 24755295]
[22]
Li J, Shen J, Zhao Y, et al. Role of miR-181a-5p in cancer (Review). Int J Oncol 2023; 63(4): 108.
[http://dx.doi.org/10.3892/ijo.2023.5556] [PMID: 37539738]
[23]
Sun W, Wang X, Li J, et al. MicroRNA-181a promotes angiogenesis in colorectal cancer by targeting SRCIN1 to promote the SRC/VEGF signaling pathway. Cell Death Dis 2018; 9(4): 438.
[http://dx.doi.org/10.1038/s41419-018-0490-4] [PMID: 29739921]
[24]
Nohata N, Hanazawa T, Enokida H, Seki N. microRNA-1/133a and microRNA-206/133b clusters: Dysregulation and functional roles in human cancers. Oncotarget 2012; 3(1): 9-21.
[http://dx.doi.org/10.18632/oncotarget.424] [PMID: 22308266]
[25]
Yu J, Xu J, Zhao J, Zhang R. Serum miR-133b is a potential novel prognostic biomarker for colorectal cancer. Int J Clin Exp Pathol 2017; 10(12): 11673-8.
[PMID: 31966526]
[26]
Liu X, Zheng W, Zhang X, Dong M, Sun G. The diagnostic and prognostic value of serum miR-206 in colorectal cancer. Int J Clin Exp Pathol 2017; 10(7): 7528-33.
[PMID: 31966596]
[27]
Rasheed Z. Bioinformatics approach: A powerful tool for microRNA research. Int J Health Sci 2017; 11(3): 1-3.
[PMID: 28936142]
[28]
Cekaite L, Eide PW, Lind GE, Skotheim RI, Lothe RA. MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer. Oncotarget 2016; 7(6): 6476-505.
[http://dx.doi.org/10.18632/oncotarget.6390] [PMID: 26623728]
[29]
Huang HY, Lin YCD, Cui S, et al. miRTarBase update 2022: An informative resource for experimentally validated miRNA–target interactions. Nucleic Acids Res 2022; 50(D1): D222-30.
[http://dx.doi.org/10.1093/nar/gkab1079] [PMID: 34850920]
[30]
Acunzo M, Romano G, Nigita G, et al. Selective targeting of point-mutated KRAS through artificial microRNAs. Proc Natl Acad Sci 2017; 114(21): E4203-12.
[http://dx.doi.org/10.1073/pnas.1620562114] [PMID: 28484014]
[31]
Tsai YS, Chareddy YS, Price BA, Parker JS, Pecot CV. An integrated model for predicting KRAS dependency. PLOS Comput Biol 2023; 19(5): e1011095.
[http://dx.doi.org/10.1371/journal.pcbi.1011095] [PMID: 37141389]
[32]
Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008; 18(10): 997-1006.
[http://dx.doi.org/10.1038/cr.2008.282] [PMID: 18766170]
[33]
Fadaka AO, Pretorius A, Klein A. Biomarkers for stratification in colorectal cancer: MicroRNAs. Cancer Contr 2019; 26(1)
[http://dx.doi.org/10.1177/1073274819862784] [PMID: 31431043]
[34]
Brase JC, Wuttig D, Kuner R, Sültmann H. Serum microRNAs as non-invasive biomarkers for cancer. Mol Cancer 2010; 9(1): 306.
[http://dx.doi.org/10.1186/1476-4598-9-306] [PMID: 21110877]
[35]
Wittmann J, Jäck HM. Serum microRNAs as powerful cancer biomarkers. Biochim Biophys Acta 2010; 1806(2): 200-7.
[PMID: 20637263]
[36]
Slaby O. Non-coding RNAs as biomarkers for colorectal cancer screening and early detection. Adv Exp Med Biol 2016; 937: 153-70.
[http://dx.doi.org/10.1007/978-3-319-42059-2_8] [PMID: 27573899]
[37]
Hollis M, Nair K, Vyas A, Chaturvedi LS, Gambhir S, Vyas D. MicroRNAs potential utility in colon cancer: Early detection, prognosis, and chemosensitivity. World J Gastroenterol 2015; 21(27): 8284-92.
[http://dx.doi.org/10.3748/wjg.v21.i27.8284] [PMID: 26217080]
[38]
Vychytilova-Faltejskova P, Radova L, Sachlova M, et al. Serum-based microRNA signatures in early diagnosis and prognosis prediction of colon cancer. Carcinogenesis 2016; 37(10): 941-50.
[http://dx.doi.org/10.1093/carcin/bgw078] [PMID: 27485599]
[39]
Sundarbose K, Kartha R, Subramanian S. MicroRNAs as biomarkers in cancer. Diagnostics 2013; 3(1): 84-104.
[http://dx.doi.org/10.3390/diagnostics3010084] [PMID: 26835669]
[40]
Hofsli E, Sjursen W, Prestvik WS, et al. Identification of serum microRNA profiles in colon cancer. Br J Cancer 2013; 108(8): 1712-9.
[http://dx.doi.org/10.1038/bjc.2013.121] [PMID: 23558896]
[41]
Niu Y, Wu Y, Huang J, Li Q, Kang K, Qu J, et al. Identification of reference genes for circulating microRNA analysis in colorectal cancer. Sci Rep 2016; 6: 35611.
[http://dx.doi.org/10.1038/srep35611]
[42]
To KKW, Tong CWS, Wu M, Cho WCS. MicroRNAs in the prognosis and therapy of colorectal cancer: From bench to bedside. World J Gastroenterol 2018; 24(27): 2949-73.
[http://dx.doi.org/10.3748/wjg.v24.i27.2949] [PMID: 30038463]
[43]
Caporali S, Calabrese C, Minieri M, et al. The miR-133a, TPM4 and TAp63γ; role in myocyte differentiation microfilament remodeling and colon cancer progression. Int J Mol Sci 2021; 22(18): 9818.
[http://dx.doi.org/10.3390/ijms22189818] [PMID: 34575979]
[44]
Lyu J, Sun Y, Li X, Ma H. MicroRNA 206 inhibits the proliferation, migration and invasion of colorectal cancer cells by regulating the c-Met/AKT/GSK-3β pathway. Oncol Lett 2020; 21(2): 147.
[http://dx.doi.org/10.3892/ol.2020.12408] [PMID: 33633805]
[45]
Hua YT, Xu WX, Li H, Xia M. Emerging roles of MiR-133a in human cancers. J Cancer 2021; 12(1): 198-206.
[http://dx.doi.org/10.7150/jca.48769] [PMID: 33391416]
[46]
Meng X, Fu R. miR-206 regulates 5-FU resistance by targeting Bcl-2 in colon cancer cells. OncoTargets Ther 2018; 11: 1757-65.
[http://dx.doi.org/10.2147/OTT.S159093] [PMID: 29636622]
[47]
Khalilian S, Hosseini Imani SZ, Ghafouri-Fard S. Emerging roles and mechanisms of miR-206 in human disorders: A comprehensive review. Cancer Cell Int 2022; 22(1): 412.
[http://dx.doi.org/10.1186/s12935-022-02833-2] [PMID: 36528620]
[48]
Xie B, Gong N, Guo Y, Hu G. MicroRNA-133b expression inversely correlates with MET and can serve as an optimum predictive biomarker for patients of colorectal cancer. Transl Cancer Res 2021; 10(1): 57-64.
[http://dx.doi.org/10.21037/tcr-20-2370] [PMID: 35116239]
[49]
Liu S, Li S, Yu X, Wang Q, Sun H. microRNA-133b represses the progression of lung cancer through inhibiting SOX9/β-catenin signaling pathway. Int J Clin Exp Pathol 2020; 13(9): 2270-9.
[PMID: 33042331]
[50]
Duan FT, Qian F, Fang K, Lin KY, Wang WT, Chen YQ. miR-133b, a muscle-specific microRNA, is a novel prognostic marker that participates in the progression of human colorectal cancer via regulation of CXCR4 expression. Mol Cancer 2013; 12(1): 164.
[http://dx.doi.org/10.1186/1476-4598-12-164] [PMID: 24330809]
[51]
Yao B, Zhang Q, Yang Z, et al. CircEZH2/miR-133b/IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of m6A-modified CREB1 mRNA. Mol Cancer 2022; 21(1): 140.
[http://dx.doi.org/10.1186/s12943-022-01608-7] [PMID: 35773744]
[52]
Wei S, Hu W, Feng J, Geng Y. Promotion or remission: A role of noncoding RNAs in colorectal cancer resistance to anti-EGFR therapy. Cell Commun Signal 2022; 20(1): 150.
[http://dx.doi.org/10.1186/s12964-022-00960-x]
[53]
Jung E, Choi J, Kim JS, Han TS. MicroRNA-based therapeutics for drug-resistant colorectal cancer. Pharmaceuticals 2021; 14(2): 136.
[http://dx.doi.org/10.3390/ph14020136] [PMID: 33567635]
[54]
Wang XW, Xi XQ, Wu J, Wan YY, Hui HX, Cao XF. microRNA-206 attenuates tumor proliferation and migration involving the downregulation of NOTCH3 in colorectal cancer. Oncol Rep 2015; 33(3): 1402-10.
[http://dx.doi.org/10.3892/or.2015.3731] [PMID: 25607234]
[55]
Yang Y, Meng WJ, Wang ZQ. MicroRNAs (miRNAs): Novel potential therapeutic targets in colorectal cancer. Front Oncol 2022; 12: 1054846.
[http://dx.doi.org/10.3389/fonc.2022.1054846] [PMID: 36591525]
[56]
Zhang C, Sun C, Zhao Y, Wang Q, Guo J, Ye B, et al. Overview of microRNAs as diagnostic and prognostic biomarkers for high-incidence cancers in 2021. Int J Mol Sci 2022; 23(19): 11389.
[57]
Sur D, Advani S, Braithwaite D. MiroRNA panels as diagnostic biomarkers for colorectal cancer: A systemic review and meta-analysis. Front Med 2022; 9(915226): 1-15.
[58]
Vega AB, Pericay C, Moya I, et al. microRNA expression profile in stage III colorectal cancer: Circulating miR-18a and miR-29a as promising biomarkers. Oncol Rep 2013; 30(1): 320-6.
[http://dx.doi.org/10.3892/or.2013.2475] [PMID: 23673725]
[59]
Ding X, Du J, Mao K, Wang X, Ding Y, Wang F. MicroRNA-143-3p suppresses tumorigenesis by targeting catenin-δ1 in colorectal cancer. OncoTargets Ther 2019; 12: 3255-65.
[http://dx.doi.org/10.2147/OTT.S184118] [PMID: 31118676]
[60]
Wei QD, Zheng WB, Sun K, Xue Q, Yang CZ, Li GX. MiR-92a promotes the invasion and migration of colorectal cancer by targeting RECK. Int J Clin Exp Pathol 2019; 12(5): 1565-77.
[PMID: 31933974]
[61]
De Palma FDE, Luglio G, Tropeano FP, Pagano G, D’Armiento M, Kroemer G, et al. The role of micro-RNAs and circulating tumor markers as predictors of response to neoadjuvant therapy in locally advanced rectal cancer. Int J Mol Sci 2020; 21(19): 7040.
[http://dx.doi.org/10.3390/ijms21197040]
[62]
Jung G, Hernández-Illán E, Moreira L, Balaguer F, Goel A. Epigenetics of colorectal cancer: Biomarker and therapeutic potential. Nat Rev Gastroenterol Hepatol 2020; 17(2): 111-30.
[http://dx.doi.org/10.1038/s41575-019-0230-y] [PMID: 31900466]
[63]
Ahadi A. The significance of microRNA deregulation in colorectal cancer development and the clinical uses as a diagnostic and prognostic biomarker and therapeutic agent. Noncoding RNA Res 2020; 5(3): 125-34.
[http://dx.doi.org/10.1016/j.ncrna.2020.08.003]
[64]
Ristau J, Staffa J, Schrotz-King P, et al. Suitability of circulating miRNAs as potential prognostic markers in colorectal cancer. Cancer Epidemiol Biomarkers Prev 2014; 23(12): 2632-7.
[http://dx.doi.org/10.1158/1055-9965.EPI-14-0556] [PMID: 25472670]
[65]
Ma M, Li L, Long F, Xiao H, Lu M, Lin C. MiR-133b inhibits colorectal cancer metastasis via lncRNA-LUCAT1. Future Oncol 2021; 17(9): 1013-23.
[http://dx.doi.org/10.2217/fon-2020-0420] [PMID: 33541136]
[66]
Jia Z, An J, Liu Z, Zhang F. Non-coding RNAs in colorectal cancer: Their functions and mechanisms. Front Oncol 2022; 12: 783079.
[http://dx.doi.org/10.3389/fonc.2022.783079] [PMID: 35186731]
[67]
Calvo-López T, Paz-Cabezas M, Llovet P, et al. Association of miR-21 and miR-335 to microsatellite instability and prognosis in stage III colorectal cancer. Cancer Biomark 2022; 34(2): 201-10.
[http://dx.doi.org/10.3233/CBM-210353] [PMID: 34958006]
[68]
Yalav O, Sonmezler O, Erdogan KE, et al. Pre-operative neo-adjuvant chemotherapy-related miRNAs as key regulators and therapeutic targets in colorectal cancer. Curr Aging Sci 2023.
[http://dx.doi.org/10.217/1874609816666230816152744] [PMID: 37723961]
[69]
Chen B, Ma Y, Bi J, et al. Regulation network of colorectal-cancer-specific enhancers in the progression of colorectal cancer. Int J Mol Sci 2021; 22(15): 8337.
[http://dx.doi.org/10.3390/ijms22158337] [PMID: 34361106]
[70]
Sahu SS, Dey S, Nabinger SC, et al. The role and therapeutic Potential of miRNAs in colorectal liver metastasis. Sci Rep 2019; 9(1): 15803.
[http://dx.doi.org/10.1038/s41598-019-52225-2] [PMID: 31676795]
[71]
Zygulska AL, Pierzchalski P. Novel diagnostic biomarkers in colorectal cancer. Int J Mol Sci 2022; 23(2): 852.
[http://dx.doi.org/10.3390/ijms23020852] [PMID: 35055034]
[72]
Hernández R, Sánchez-Jiménez E, Melguizo C, Prados J, Rama AR. Downregulated microRNAs in the colorectal cancer: Diagnostic and therapeutic perspectives. BMB Rep 2018; 51(11): 563-71.
[http://dx.doi.org/10.5483/BMBRep.2018.51.11.116] [PMID: 30158023]
[73]
Lee J, Hong HK, Peng SB, et al. Identifying metastasis-initiating miRNA-target regulations of colorectal cancer from expressional changes in primary tumors. Sci Rep 2020; 10(1): 14919.
[http://dx.doi.org/10.1038/s41598-020-71868-0] [PMID: 32913235]
[74]
Ogunwobi OO, Mahmood F, Akingboye A. Biomarkers in colorectal cancer: Current research and prospects. Int J Mol Sci 2020; 21(15): 5311.
[http://dx.doi.org/10.3390/ijms21155311] [PMID: 32726923]
[75]
Pidíkova P, Reis R, Herichova I. miRNA clusters with down-regulated expression in human colorectal cancer and their regulation. Int J Mol Sci 2020; 21(13): 4633.
[http://dx.doi.org/10.3390/ijms21134633] [PMID: 32610706]

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