Overexpression of miR‑106a enhances oxaliplatin sensitivity of colorectal cancer through regulation of FOXQ1

Liu,Zhihu; Qin,Yan; Dong,Shuxiao; Chen,Xiao; Huo,Zhibin; Zhen,Zhongguang

doi:10.3892/ol.2019.11151

Overexpression of miR‑106a enhances oxaliplatin sensitivity of colorectal cancer through regulation of FOXQ1

Authors:
- Zhihu Liu
- Yan Qin
- Shuxiao Dong
- Xiao Chen
- Zhibin Huo
- Zhongguang Zhen
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Affiliations: Department of Hepatobiliary Surgery, Xingtai People's Hospital, Xingtai, Hebei 054000, P.R. China, Surgical Department of Gastrointestinal Neoplasms, Xingtai People's Hospital, Xingtai, Hebei 054000, P.R. China, Obstetrical Department, Xingtai Third Hospital, Xingtai, Hebei 054000, P.R. China, Department of Anesthesiology, Xingtai People's Hospital, Xingtai, Hebei 054000, P.R. China
Published online on: November 28, 2019 https://doi.org/10.3892/ol.2019.11151
Pages: 663-670
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chemotherapy resistance poses a major challenge for the clinical treatment of colorectal cancer, therefore, the aim of the present study was to examine its underlying mechanisms. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were used to determine the microRNA (miRNA)/mRNA and protein expression levels, respectively. A dual luciferase assay was conducted for verification of the interaction between miR‑106a and 3'untranslated region (UTR) of Forkhead box Q1 (FOXQ1). Cell viability was assessed using an MTT assay. In the present study, it was demonstrated that miR‑106a is involved in regulating oxaliplatin sensitivity of colorectal cancer. Transfection of miR‑106a mimics slightly inhibited colorectal cancer cell growth and sensitized colorectal cancer cells to oxaliplatin exposure. In addition, miR‑106a overexpression induced a decrease of FOXQ1 at mRNA and protein levels in colorectal cancer cells. The enhanced expression of miR‑106a also increased the expression of Wnt target genes, including vascular endothelial growth factor‑A and matrix metallopeptidase 2, which were reported to be regulated by FOXQ1. It was predicted and validated that miR‑106a could repress FOXQ1 expression via direct binding to 3'UTR. Elevation of miR‑106a and a decrease of FOXQ1 expression levels were detected in tumor tissues from patients with oxaliplatin‑sensitive colorectal cancer, compared with patients with oxaliplatin‑resistant colorectal cancer. Furthermore, there was a significant association between miR‑106a and FOXQ1 mRNA levels. In conclusion, the present study demonstrated that miR‑106a increased oxaliplatin sensitivity of colorectal cancer cells through direct repression of FOXQ1 expression.

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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	André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, et al: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 350:2343–2351. 2004. View Article : Google Scholar : PubMed/NCBI
3	Raymond E, Faivre S, Chaney S, Woynarowski J and Cvitkovic E: Cellular and molecular pharmacology of oxaliplatin. Mol Cancer Ther. 1:227–235. 2002.PubMed/NCBI
4	Rabik CA and Dolan ME: Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev. 33:9–23. 2007. View Article : Google Scholar : PubMed/NCBI
5	Ambros V: microRNAs: Tiny regulators with great potential. Cell. 107:823–826. 2001. View Article : Google Scholar : PubMed/NCBI
6	Ardekani AM and Naeini MM: The role of microRNAs in human diseases. Avicenna J Med Biotechnol. 2:161–179. 2010.PubMed/NCBI
7	Du B, Wu D, Yang X, Wang T, Shi X, Lv Y, Zhou Z, Liu Q and Zhang W: The expression and significance of microRNA in different stages of colorectal cancer. Medicine (Baltimore). 97:e96352018. View Article : Google Scholar : PubMed/NCBI
8	Emami SS, Akbari A, Zare AA, Agah S, Masoodi M, Talebi A, Minaeian S, Fattahi A and Moghadamnia F: MicroRNA expression levels and histopathological features of colorectal cancer. J Gastrointest Cancer. 50:276–284. 2019. View Article : Google Scholar : PubMed/NCBI
9	Zhang Y, Hu X, Miao X, Zhu K, Cui S, Meng Q, Sun J and Wang T: MicroRNA-425-5p regulates chemoresistance in colorectal cancer cells via regulation of programmed cell death 10. J Cell Mol Med. 20:360–369. 2016. View Article : Google Scholar : PubMed/NCBI
10	Zhou Y, Wan G, Spizzo R, Ivan C, Mathur R, Hu X, Ye X, Lu J, Fan F, Xia L, et al: miR-203 induces oxaliplatin resistance in colorectal cancer cells by negatively regulating ATM kinase. Mol Oncol. 8:83–92. 2014. View Article : Google Scholar : PubMed/NCBI
11	Ayers D and Vandesompele J: Influence of microRNAs and long non-coding RNAs in cancer chemoresistance. Genes (Basel). 8(pii): E952017. View Article : Google Scholar : PubMed/NCBI
12	Feng B, Dong TT, Wang LL, Zhou HM, Zhao HC, Dong F and Zheng MH: Colorectal cancer migration and invasion initiated by microRNA-106a. PLoS One. 7:e434522012. View Article : Google Scholar : PubMed/NCBI
13	Koga Y, Yamazaki N, Yamamoto Y, Yamamoto S, Saito N, Kakugawa Y, Otake Y, Matsumoto M and Matsumura Y: Fecal miR-106a is a useful marker for colorectal cancer patients with false-negative results in immunochemical fecal occult blood test. Cancer Epidemiol Biomarkers Prev. 22:1844–1852. 2013. View Article : Google Scholar : PubMed/NCBI
14	Liu GH, Zhou ZG, Chen R, Wang MJ, Zhou B, Li Y and Sun XF: Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer. Tumour Biol. 34:2175–2181. 2013. View Article : Google Scholar : PubMed/NCBI
15	Diaz R, Silva J, Garcia JM, Lorenzo Y, García V, Peña C, Rodríguez R, Muñoz C, García F, Bonilla F and Domínguez G: Deregulated expression of miR-106a predicts survival in human colon cancer patients. Genes Chromosomes Cance. 47:794–802. 2008. View Article : Google Scholar
16	Overdier DG, Porcella A and Costa RH: The DNA-binding specificity of the hepatocyte nuclear factor 3/forkhead domain is influenced by amino-acid residues adjacent to the recognition helix. Mol Cell Biol. 14:2755–2766. 1994. View Article : Google Scholar : PubMed/NCBI
17	Zhu H: Targeting forkhead box transcription factors FOXM1 and FOXO in leukemia (Review). Oncol Rep. 32:1327–1334. 2014. View Article : Google Scholar : PubMed/NCBI
18	Kaneda H, Arao T, Tanaka K, Tamura D, Aomatsu K, Kudo K, Sakai K, De Velasco MA, Matsumoto K, Fujita Y, et al: FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth. Cancer Res. 70:2053–2063. 2010. View Article : Google Scholar : PubMed/NCBI
19	Weng W, Okugawa Y, Toden S, Toiyama Y, Kusunoki M and Goel A: FOXM1 and FOXQ1 are promising prognostic biomarkers and novel targets of tumor-suppressive miR-342 in human colorectal cancer. Clin Cancer Res. 22:4947–4957. 2016. View Article : Google Scholar : PubMed/NCBI
20	Christensen J, Bentz S, Sengstag T, Shastri VP and Anderle P: FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors. PLoS One. 8:e600512013. View Article : Google Scholar : PubMed/NCBI
21	Vishnubalaji R, Hamam R, Yue S, Al-Obeed O, Kassem M, Liu FF, Aldahmash A and Alajez NM: MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1. Oncotarget. 7:35789–35802. 2016. View Article : Google Scholar : PubMed/NCBI
22	Calnan DR and Brunet A: The FoxO code. Oncogene. 27:2276–2288. 2008. View Article : Google Scholar : PubMed/NCBI
23	Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar : PubMed/NCBI
24	Codony-Servat J, Cuatrecasas M, Asensio E, Montironi C, Martínez-Cardús A, Marín-Aguilera M, Horndler C, Martínez-Balibrea E, Rubini M, Jares P, et al: Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer. Br J Cancer. 117:1777–1786. 2017. View Article : Google Scholar : PubMed/NCBI
25	Ju HQ, Lu YX, Wu QN, Liu J, Zeng ZL, Mo HY, Chen Y, Tian T, Wang Y, Kang TB, et al: Disrupting G6PD-mediated Redox homeostasis enhances chemosensitivity in colorectal cancer. Oncogene. 36:6282–6292. 2017. View Article : Google Scholar : PubMed/NCBI
26	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
27	Peng X, Luo Z, Kang Q, Deng D, Wang Q, Peng H, Wang S and Wei Z: FOXQ1 mediates the crosstalk between TGF-β and Wnt signaling pathways in the progression of colorectal cancer. Cancer Biol Ther. 16:1099–1109. 2015. View Article : Google Scholar : PubMed/NCBI
28	Davies JM and Goldberg RM: First-line therapeutic strategies in metastatic colorectal cancer. Oncology (Williston Park). 22:1470–1479. 2008.PubMed/NCBI
29	Hector S, Bolanowska-Higdon W, Zdanowicz J, Hitt S and Pendyala L: In vitro studies on the mechanisms of oxaliplatin resistance. Cancer Chemother Pharmacol. 48:398–406. 2001. View Article : Google Scholar : PubMed/NCBI
30	Li J, Chen Y, Zhao J, Kong F and Zhang Y: miR-203 reverses chemoresistance in p53-mutated colon cancer cells through downregulation of Akt2 expression. Cancer Lett. 304:52–59. 2011. View Article : Google Scholar : PubMed/NCBI
31	Sau A, Pellizzari Tregno F, Valentino F, Federici G and Caccuri AM: Glutathione transferases and development of new principles to overcome drug resistance. Arch Biochem Biophys. 500:116–122. 2010. View Article : Google Scholar : PubMed/NCBI
32	Thomas J, Ohtsuka M, Pichler M and Ling H: MicroRNAs: Clinical relevance in colorectal cancer. Int J Mol Sci. 16:28063–28076. 2015. View Article : Google Scholar : PubMed/NCBI
33	Bovell LC, Shanmugam C, Putcha BD, Katkoori VR, Zhang B, Bae S, Singh KP, Grizzle WE and Manne U: The prognostic value of microRNAs varies with patient race/ethnicity and stage of colorectal cancer. Clin Cancer Res. 19:3955–3965. 2013. View Article : Google Scholar : PubMed/NCBI
34	Li J, Liu Y, Wang C, Deng T, Liang H, Wang Y, Huang D, Fan Q, Wang X, Ning T, et al: Serum miRNA expression profile as a prognostic biomarker of stage II/III colorectal adenocarcinoma. Sci Rep. 5:129212015. View Article : Google Scholar : PubMed/NCBI
35	Qin Y, Huo Z, Song X, Chen X, Tian X and Wang X: mir-106a regulates cell proliferation and apoptosis of colon cancer cells through targeting the PTEN/PI3K/AKT signaling pathway. Oncol Lett. 15:3197–3201. 2018.PubMed/NCBI
36	Hao H, Liu L, Zhang D, Wang C, Xia G, Zhong F and Hu X: Diagnostic and prognostic value of miR-106a in colorectal cancer. Oncotarget. 8:5038–5047. 2017. View Article : Google Scholar : PubMed/NCBI
37	Li Y, Zhang Y, Yao Z, Li S, Yin Z and Xu M: Forkhead box Q1: A key player in the pathogenesis of tumors (Review). Int J Oncol. 49:51–58. 2016. View Article : Google Scholar : PubMed/NCBI
38	Qiao Y, Jiang X, Lee ST, Karuturi RK, Hooi SC and Yu Q: FOXQ1 regulates epithelial-mesenchymal transition in human cancers. Cancer Res. 71:3076–3086. 2011. View Article : Google Scholar : PubMed/NCBI