MicroRNA-141 inhibits tumor growth and minimizes therapy resistance in colorectal cancer

Ye,Jun; Wang,Zhen; Zhao,Jing; Chen,Wuzhen; Wu,Dang; Wu,Pin; Huang,Jian

doi:10.3892/mmr.2017.6135

MicroRNA-141 inhibits tumor growth and minimizes therapy resistance in colorectal cancer

Authors:
- Jun Ye
- Zhen Wang
- Jing Zhao
- Wuzhen Chen
- Dang Wu
- Pin Wu
- Jian Huang
View Affiliations

Affiliations: Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China, Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang), Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China, Department of Thoracic Surgury, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China, Department of Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
Published online on: January 23, 2017 https://doi.org/10.3892/mmr.2017.6135
Pages: 1037-1042
Copyright: © Ye et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Colorectal cancer (CRC) is one of most common cancers and causes of cancer-associated mortality worldwide, due to its recurrence, metastasis and therapy resistance. Cancer stem cells (CSC) have been demonstrated to be vital for tumor initiation and recurrence. microRNAs may act as an oncogenes or tumor suppressors in numerous cancers. The present study demonstrated that microRNA-141 (miR‑141) was downregulated in CSC compared with differentiated cancer cells, and in tumor compared with healthy tissue. miR‑141 may inhibit CRC cell proliferation and the maintenance of CSC stemness, thereby enhancing drug susceptibility. In addition, the present study identified cyclin D2 as a novel target gene of miR‑141. In conclusion, the antitumor role of miR‑141 and its target cyclin D2 may suggest the development of miR‑141 as a potential therapeutic agent.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP and Stassi G: Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 1:389–402. 2007. View Article : Google Scholar : PubMed/NCBI
3	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
4	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
5	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
6	Ma S, Tang KH, Chan YP, Lee TK, Kwan PS, Castilho A, Ng I, Man K, Wong N, To KF, et al: miR-130b Promotes CD133(+) liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell. 7:694–707. 2010. View Article : Google Scholar : PubMed/NCBI
7	Visvader JE and Lindeman GJ: Cancer stem cells in solid tumours: Accumulating evidence and unresolved questions. Nat Rev Cancer. 8:755–768. 2008. View Article : Google Scholar : PubMed/NCBI
8	Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, et al: Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA. 104:10158–10163. 2007. View Article : Google Scholar : PubMed/NCBI
9	Yin S, Li J, Hu C, Chen X, Yao M, Yan M, Jiang G, Ge C, Xie H, Wan D, et al: CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int J Cancer. 120:1444–1450. 2007. View Article : Google Scholar : PubMed/NCBI
10	Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV and Varticovski L: Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics. Breast Cancer Res. 10:R102008. View Article : Google Scholar : PubMed/NCBI
11	Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD and Dirks PB: Identification of human brain tumour initiating cells. Nature. 432:396–401. 2004. View Article : Google Scholar : PubMed/NCBI
12	Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C and De Maria R: Identification and expansion of human colon-cancer-initiating cells. Nature. 445:111–115. 2007. View Article : Google Scholar : PubMed/NCBI
13	Olempska M, Eisenach PA, Ammerpohl O, Ungefroren H, Fandrich F and Kalthoff H: Detection of tumor stem cell markers in pancreatic carcinoma cell lines. Hepatobiliary Pancreat Dis Int. 6:92–97. 2007.PubMed/NCBI
14	Collins AT, Berry PA, Hyde C, Stower MJ and Maitland NJ: Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 65:10946–10951. 2005. View Article : Google Scholar : PubMed/NCBI
15	Bhatia M: AC133 expression in human stem cells. Leukemia. 15:1685–1688. 2001. View Article : Google Scholar : PubMed/NCBI
16	Wang YK, Zhu YL, Qiu FM, Zhang T, Chen ZG, Zheng S and Huang J: Activation of Akt and MAPK pathways enhances the tumorigenicity of CD133+ primary colon cancer cells. Carcinogenesis. 31:1376–1380. 2010. View Article : Google Scholar : PubMed/NCBI
17	Xu L, Li Q, Xu D, Wang Q, An Y, Du Q, Zhang J, Zhu Y and Miao Y: hsa-miR-141 downregulates TM4SF1 to inhibit pancreatic cancer cell invasion and migration. Int J Oncol. 44:459–466. 2014.PubMed/NCBI
18	Grimholt RM, Urdal P, Klingenberg O and Piehler AP: Rapid and reliable detection of alpha-globin copy number variations by quantitative real-time PCR. BMC Hematol. 14:42014. View Article : Google Scholar : PubMed/NCBI
19	Dalerba P, Cho RW and Clarke MF: Cancer stem cells: Models and concepts. Annu Rev Med. 58:267–284. 2007. View Article : Google Scholar : PubMed/NCBI
20	Wang Z, Oron E, Nelson B, Razis S and Ivanova N: Distinct lineage specification roles for NANOG, OCT4 and SOX2 in human embryonic stem cells. Cell Stem Cell. 10:440–454. 2012. View Article : Google Scholar : PubMed/NCBI
21	Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, Egan DA, Li A, Huang G, Klein-Szanto AJ, et al: The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol. 10:202–210. 2008. View Article : Google Scholar : PubMed/NCBI
22	Yamada N, Tsujimura N, Kumazaki M, Shinohara H, Taniguchi K, Nakagawa Y, Naoe T and Akao Y: Colorectal cancer cell-derived microvesicles containing microRNA-1246 promote angiogenesis by activating Smad 1/5/8 signaling elicited by PML down-regulation in endothelial cells. Biochim Biophys Acta. 1839:1256–1272. 2014. View Article : Google Scholar : PubMed/NCBI
23	Sun HB, Chen X, Ji H, Wu T, Lu HW, Zhang Y, Li H and Li YM: miR-494 is an independent prognostic factor and promotes cell migration and invasion in colorectal cancer by directly targeting PTEN. Int J Oncol. 45:2486–2494. 2014.PubMed/NCBI
24	Wang B, Li W, Liu H, Yang L, Liao Q, Cui S, Wang H and Zhao L: miR-29b suppresses tumor growth and metastasis in colorectal cancer via downregulating Tiam1 expression and inhibiting epithelial-mesenchymal transition. Cell Death Dis. 5:e13352014. View Article : Google Scholar : PubMed/NCBI
25	Zhang J, Fei B, Wang Q, Song M, Yin Y, Zhang B, Ni S, Guo W, Bian Z, Quan C, et al: MicroRNA-638 inhibits cell proliferation, invasion and regulates cell cycle by targeting tetraspanin 1 in human colorectal carcinoma. Oncotarget. 5:12083–12096. 2014. View Article : Google Scholar : PubMed/NCBI
26	Yu G, Li H, Wang X, Wu T, Zhu J, Huang S, Wan Y and Tang J: MicroRNA-19a targets tissue factor to inhibit colon cancer cells migration and invasion. Mol Cell Biochem. 380:239–247. 2013. View Article : Google Scholar : PubMed/NCBI
27	Chen MB, Yang L, Lu PH, Fu XL, Zhang Y, Zhu YQ and Tian Y: MicroRNA-101 down-regulates sphingosine kinase 1 in colorectal cancer cells. Biochem Biophys Res Commun. 463:954–960. 2015. View Article : Google Scholar : PubMed/NCBI
28	Meyyappan M, Wong H, Hull C and Riabowol KT: Increased expression of cyclin D2 during multiple states of growth arrest in primary and established cells. Mol Cell Biol. 18:3163–3172. 1998. View Article : Google Scholar : PubMed/NCBI
29	Becker KA, Ghule PN, Lian JB, Stein JL, van Wijnen AJ and Stein GS: Cyclin D2 and the CDK substrate p220 (NPAT) are required for self-renewal of human embryonic stem cells. J Cell Physiol. 222:456–464. 2010. View Article : Google Scholar : PubMed/NCBI
30	Wang J, Yang M, Li Y and Han B: The role of MicroRNAs in the chemoresistance of breast cancer. Drug Dev Res. 76:368–374. 2015. View Article : Google Scholar : PubMed/NCBI