Upregulation of miR-101 enhances the cytotoxic effect of anticancer drugs through inhibition of colon cancer cell proliferation

Chen,Le-Gao; Xia,Ying-Jie; Cui,Ying

doi:10.3892/or.2017.5666

Upregulation of miR-101 enhances the cytotoxic effect of anticancer drugs through inhibition of colon cancer cell proliferation

Authors:
- Le-Gao Chen
- Ying-Jie Xia
- Ying Cui
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Affiliations: Department of Vascular Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China, Key Laboratory of Gastroenterology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China, Department of Unclear Medicine, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
Published online on: May 24, 2017 https://doi.org/10.3892/or.2017.5666
Pages: 100-108
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

This study investigated the effect of miR-101 on proliferation, migration, invasion, and chemotherapy sensitivity in colon cancer cell lines HT-29 and RKO. MicroRNAs are a class of small noncoding RNA molecules, which play important roles in diverse biological processes of human cancers, such as carcinogenesis, development, differentiation, and apoptosis. The expression of miR-101 in colon cancer and adjacent non-tumor tissues were examined by quantitative real-time polymerase chain reaction. The expression of miR-101 was upregulated by recombinant adenovirus Ad-miR-101. Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cloning methods. Cell migration and invasion potential were examined using Transwell migration and Matrigel invasion chamber assays. Drug sensitivity to 5-fluorouracil (5-FU) and cisplatin (DDP) was explored using MTT assays and l acridine orange/ethidium bromide double staining. The expression of miR-101 decreased in colon cancer tissues compared with adjacent non-tumor tissues. The upregulated expression of miR-101 suppressed cell proliferation and inhibited cell migration and invasion in HT-29 and RKO colon cancer cell lines. The overexpression of miR-101 promoted the inhibitory effect of 5-FU and DDP on HT-29 cells. The expression of miR-101 was downregulated in colon cancer. The upregulated expression of miR-101 inhibited proliferation and migration, and increased the sensitivity of colon cancer cells to chemotherapy.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Sjo OH, Berg M, Merok MA, Kolberg M, Svindland A, Lothe RA and Nesbakken A: Peritoneal carcinomatosis of colon cancer origin: Highest incidence in women and in patients with right-sided tumors. J Surg Oncol. 104:792–797. 2011. View Article : Google Scholar : PubMed/NCBI
3	Mori F, Ferraiuolo M, Santoro R, Sacconi A, Goeman F, Pallocca M, Pulito C, Korita E, Fanciulli M, Muti P, et al: Multitargeting activity of miR-24 inhibits long-term melatonin anticancer effects. Oncotarget. 7:20532–20548. 2016.PubMed/NCBI
4	Patel Y, Shah N, Lee JS, Markoutsa E, Jie C, Liu S, Botbyl R, Reisman D, Xu P and Chen H: A novel double-negative feedback loop between miR-489 and the HER2-SHP2-MAPK signaling axis regulates breast cancer cell proliferation and tumor growth. Oncotarget. 7:18295–18308. 2016.PubMed/NCBI
5	Konishi H, Fujiya M, Ueno N, Moriichi K, Sasajima J, Ikuta K, Tanabe H, Tanaka H and Kohgo Y: microRNA-26a and −584 inhibit the colorectal cancer progression through inhibition of the binding of hnRNP A1-CDK6 mRNA. Biochem Biophys Res Commun. 467:847–852. 2015. View Article : Google Scholar : PubMed/NCBI
6	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
7	Farazi TA, Spitzer JI, Morozov P and Tuschl T: miRNAs in human cancer. J Pathol. 223:102–115. 2011. View Article : Google Scholar : PubMed/NCBI
8	Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, et al: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:2999–3004. 2004. View Article : Google Scholar : PubMed/NCBI
9	Chauhan R and Lahiri N: Tissue- and serum-associated biomarkers of hepatocellular carcinoma. Biomark Cancer. 8 Suppl 1:37–55. 2016. View Article : Google Scholar : PubMed/NCBI
10	Suárez-Arriaga MC, Ribas-Aparicio RM and Ruiz-Tachiquín ME: MicroRNAs in hereditary diffuse gastric cancer. Biomed Rep. 5:151–154. 2016.PubMed/NCBI
11	Mohamad M, Wahab NA, Yunus R, Murad NA, Zainuddin ZM, Sundaram M and Mokhtar NM: Roles of microRNA21 and microRNA29a in regulating cell adhesion related genes in bone metastasis secondary to prostate cancer. Asian Pac J Cancer Prev. 17:3437–3445. 2016.PubMed/NCBI
12	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
13	Mukohyama J, Shimono Y, Yamashita K, Sumi Y, Mukohara T, Minami H and Kakeji Y: Effect of xenotransplantation site on microRNA expression of human colon cancer stem cells. Anticancer Res. 36:3679–3686. 2016.PubMed/NCBI
14	Kumar S, Nag A and Mandal CC: A comprehensive review on miR-200c, a promising cancer biomarker with therapeutic potential. Curr Drug Targets. 16:1381–1403. 2015. View Article : Google Scholar : PubMed/NCBI
15	Eyking A, Reis H, Frank M, Gerken G, Schmid KW and Cario E: MiR-205 and miR-373 are associated with aggressive human mucinous colorectal cancer. PLoS One. 11:e01568712016. View Article : Google Scholar : PubMed/NCBI
16	Vella S, Pomella S, Leoncini PP, Colletti M, Conti B, Marquez VE, Strillacci A, Roma J, Gallego S, Milano GM, et al: MicroRNA-101 is repressed by EZH2 and its restoration inhibits tumorigenic features in embryonal rhabdomyosarcoma. Clin Epigenetics. 7:822015. View Article : Google Scholar : PubMed/NCBI
17	Konno Y, Dong P, Xiong Y, Suzuki F, Lu J, Cai M, Watari H, Mitamura T, Hosaka M, Hanley SJ, et al: MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells. Oncotarget. 5:6049–6062. 2014. View Article : Google Scholar : PubMed/NCBI
18	Xu L, Beckebaum S, Iacob S, Wu G, Kaiser GM, Radtke A, Liu C, Kabar I, Schmidt HH, Zhang X, et al: MicroRNA-101 inhibits human hepatocellular carcinoma progression through EZH2 downregulation and increased cytostatic drug sensitivity. J Hepatol. 60:590–598. 2014. View Article : Google Scholar : PubMed/NCBI
19	Kopczyńska E: Role of microRNAs in the resistance of prostate cancer to docetaxel and paclitaxel. Contemp Oncol (Pozn). 19:423–427. 2015.PubMed/NCBI
20	Vanas V, Haigl B, Stockhammer V and Sutterlüty-Fall H: MicroRNA-21 increases proliferation and cisplatin sensitivity of osteosarcoma-derived cells. PLoS One. 11:e01610232016. View Article : Google Scholar : PubMed/NCBI
21	Zhao H, Yu X, Ding Y, Zhao J, Wang G, Wu X, Jiang J, Peng C, Guo GZ and Cui S: MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2. Oncotarget. 7:53254–53268. 2016.PubMed/NCBI
22	Hu Y, Qiu Y, Yagüe E, Ji W, Liu J and Zhang J: miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer. Cell Death Dis. 7:e22912016. View Article : Google Scholar : PubMed/NCBI