MiR-574-5p mediates the cell cycle and apoptosis in thyroid cancer cells via Wnt/β-catenin signaling by repressing the expression of Quaking proteins

Zhang,Zhejia; Li,Xinying; Xiao,Qian; Wang,Zhiming

doi:10.3892/ol.2018.8067

MiR-574-5p mediates the cell cycle and apoptosis in thyroid cancer cells via Wnt/β-catenin signaling by repressing the expression of Quaking proteins

Authors:
- Zhejia Zhang
- Xinying Li
- Qian Xiao
- Zhiming Wang
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Affiliations: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Mental Hygiene Clinics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: February 15, 2018 https://doi.org/10.3892/ol.2018.8067
Pages: 5841-5848

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Abstract

Thyroid cancer is the most frequently occurring type of endocrine tumor, with a rapidly increasing incidence rate. MicroRNA (miR)-574-5p is a candidate oncogene in various types of cancer. The present study identified that miR‑574‑5p affected the cell cycle distribution and apoptosis of BCPAP and FTC133 thyroid cancer cells via β‑catenin/Wnt signaling by targeting Quaking proteins (QKIs). An MTT assay demonstrated that the knockdown of miR‑574‑5p suppressed the proliferation of the thyroid cancer cells. Fluorescence‑activated cell sorting analysis demonstrated that the inhibition of miR‑574‑5p induced the G1/S phase arrest and apoptosis of the cells. Reverse transcription‑quantitative polymerase chain reaction and western blot analyses revealed that the knockdown of miR‑574‑5p significantly upregulated the mRNA and protein expression levels of QKIs. Furthermore, western blot analysis identified that the knockdown of miR‑574‑5p also repressed the Wnt/β‑catenin pathway via downregulating the expression of β‑catenin, cyclin D1 and survivin, and upregulating the phosphorylation of β‑catenin. The further depletion of QKIs in combination with the knockdown of miR‑574‑5p not only increased the expression of β‑catenin, cyclin D1 and survivin, but also rescued the apoptosis of thyroid cancer cells induced by the miR‑574‑5p knockdown. In conclusion, these findings indicated that the aberrant upregulation of miR‑574‑5p may be oncogenic, through regulating the Wnt/β‑catenin pathway by targeting QKIs.

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1	Nikiforov YE: Thyroid carcinoma: Molecular pathways and therapeutic targets. Mod Pathol. 21 Suppl 2:S37–S43. 2008. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Siegel R, Ward E, Murray T, Xu J and Thun MJ: Cancer statistics, 2007. CA Cancer J Clin. 57:43–66. 2007. View Article : Google Scholar : PubMed/NCBI
3	Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW and Wiersinga W; European Thyroid Cancer Taskforce, : European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol. 154:787–803. 2006. View Article : Google Scholar : PubMed/NCBI
4	Zheng T, Holford TR, Chen Y, Ma JZ, Flannery J, Liu W, Russi M and Boyle P: Time trend and age-period-cohort effect on incidence of thyroid cancer in Connecticut, 1935–1992. Int J Cancer. 67:504–509. 1996. View Article : Google Scholar : PubMed/NCBI
5	Liu S, Semenciw R, Ugnat AM and Mao Y: Increasing thyroid cancer incidence in Canada, 1970–1996: Time trends and age-period-cohort effects. Br J Cancer. 85:1335–1339. 2001. View Article : Google Scholar : PubMed/NCBI
6	Xing M: Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 13:184–199. 2013. View Article : Google Scholar : PubMed/NCBI
7	Begum S, Rosenbaum E, Henrique R, Cohen Y, Sidransky D and Westra WH: BRAF mutations in anaplastic thyroid carcinoma: Implications for tumor origin, diagnosis and treatment. Mod Pathol. 17:1359–1363. 2004. View Article : Google Scholar : PubMed/NCBI
8	Ji S, Ye G, Zhang J, Wang L, Wang T, Wang Z, Zhang T, Wang G, Guo Z, Luo Y, et al: miR-574-5p negatively regulates Qki6/7 to impact beta-catenin/Wnt signalling and the development of colorectal cancer. Gut. 62:716–726. 2013. View Article : Google Scholar : PubMed/NCBI
9	Kondo T, Furuta T, Mitsunaga K, Ebersole TA, Shichiri M, Wu J, Artzt K, Yamamura K and Abe K: Genomic organization and expression analysis of the mouse qkI locus. Mamm Genome. 10:662–669. 1999.PubMed/NCBI
10	Pilotte J, Larocque D and Richard S: Nuclear translocation controlled by alternatively spliced isoforms inactivates the QUAKING apoptotic inducer. Genes Dev. 15:845–858. 2001. View Article : Google Scholar : PubMed/NCBI
11	Biedermann B, Hotz HR and Ciosk R: The Quaking family of RNA-binding proteins: Coordinators of the cell cycle and differentiation. Cell Cycle. 9:1929–1933. 2010. View Article : Google Scholar : PubMed/NCBI
12	Larocque D, Galarneau A, Liu HN, Scott M, Almazan G and Richard S: Protection of p27(Kip1) mRNA by quaking RNA binding proteins promotes oligodendrocyte differentiation. Nat Neurosci. 8:27–33. 2005. View Article : Google Scholar : PubMed/NCBI
13	Chénard CA and Richard S: New implications for the QUAKING RNA binding protein in human disease. J Neurosci Res. 86:233–242. 2008. View Article : Google Scholar : PubMed/NCBI
14	Yang G, Fu H, Zhang J, Lu X, Yu F, Jin L, Bai L, Huang B, Shen L, Feng Y, et al: RNA-binding protein quaking, a critical regulator of colon epithelial differentiation and a suppressor of colon cancer. Gastroenterology. 138:231–240.e1-5. 2010. View Article : Google Scholar : PubMed/NCBI
15	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
16	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
17	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
18	Fan M, Li X, Jiang W, Huang Y, Li J and Wang Z: A long non-coding RNA, PTCSC3, as a tumor suppressor and a target of miRNAs in thyroid cancer cells. Exp Ther Med. 5:1143–1146. 2013. View Article : Google Scholar : PubMed/NCBI
19	Melo SA and Esteller M: Dysregulation of microRNAs in cancer: Playing with fire. FEBS Lett. 585:2087–2099. 2011. View Article : Google Scholar : PubMed/NCBI
20	Barker N and Clevers H: Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov. 5:997–1014. 2006. View Article : Google Scholar : PubMed/NCBI
21	Futaki S, Suzuki T, Ohashi W, Yagami T, Tanaka S, Ueda K and Sugiura Y: Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J Biol Chem. 276:5836–5840. 2001. View Article : Google Scholar : PubMed/NCBI
22	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
23	Raymond CK, Roberts BS, Garrett-Engele P, Lim LP and Johnson JM: Simple, quantitative primer-extension PCR assay for direct monitoring of microRNAs and short-interfering RNAs. RNA. 11:1737–1744. 2005. View Article : Google Scholar : PubMed/NCBI
24	Galarneau A and Richard S: Target RNA motif and target mRNAs of the Quaking STAR protein. Nat Struct Mol Biol. 12:691–698. 2005. View Article : Google Scholar : PubMed/NCBI
25	Shenouda SK and Alahari SK: MicroRNA function in cancer: Oncogene or a tumor suppressor? Cancer Metastasis Rev. 28:369–378. 2009. View Article : Google Scholar : PubMed/NCBI
26	Li Q, Li X, Guo Z, Xu F, Xia J, Liu Z and Ren T: MicroRNA-574-5p was pivotal for TLR9 signaling enhanced tumor progression via down-regulating checkpoint suppressor 1 in human lung cancer. PLoS One. 7:e482782012. View Article : Google Scholar : PubMed/NCBI
27	Noveroske JK, Lai L, Gaussin V, Northrop JL, Nakamura H, Hirschi KK and Justice MJ: Quaking is essential for blood vessel development. Genesis. 32:218–230. 2002. View Article : Google Scholar : PubMed/NCBI
28	Novikov L, Park JW, Chen H, Klerman H, Jalloh AS and Gamble MJ: QKI-mediated alternative splicing of the histone variant MacroH2A1 regulates cancer cell proliferation. Mol Cell Biol. 31:4244–4255. 2011. View Article : Google Scholar : PubMed/NCBI
29	Bian Y, Wang L, Lu H, Yang G, Zhang Z, Fu H, Lu X, Wei M, Sun J, Zhao Q, et al: Downregulation of tumor suppressor QKI in gastric cancer and its implication in cancer prognosis. Biochem Biophys Res Commun. 422:187–193. 2012. View Article : Google Scholar : PubMed/NCBI
30	Zong FY, Fu X, Wei WJ, Luo YG, Heiner M, Cao LJ, Fang Z, Fang R, Lu D, Ji H and Hui J: The RNA-binding protein QKI suppresses cancer-associated aberrant splicing. PLoS Genet. 10:e10042892014. View Article : Google Scholar : PubMed/NCBI
31	He Z, Yi J, Liu X, Chen J, Han S, Jin L, Chen L and Song H: MiR-143-3p functions as a tumor suppressor by regulating cell proliferation, invasion and epithelial-mesenchymal transition by targeting QKI-5 in esophageal squamous cell carcinoma. Mol Cancer. 15:512016. View Article : Google Scholar : PubMed/NCBI
32	Miyoshi K, Rosner A, Nozawa M, Byrd C, Morgan F, Landesman-Bollag E, Xu X, Seldin DC, Schmidt EV, Taketo MM, et al: Activation of different Wnt/beta-catenin signaling components in mammary epithelium induces transdifferentiation and the formation of pilar tumors. Oncogene. 21:5548–5556. 2002. View Article : Google Scholar : PubMed/NCBI
33	Wieczorek M, Paczkowska A, Guzenda P, Majorek M, Bednarek AK and Lamparska-Przybysz M: Silencing of Wnt-1 by siRNA induces apoptosis of MCF-7 human breast cancer cells. Cancer Biol Ther. 7:268–274. 2008. View Article : Google Scholar : PubMed/NCBI