MicroRNA‑216a‑5p suppresses esophageal squamous cell carcinoma progression by targeting KIAA0101

Sun,Tuanhe; An,Qi; Yan,Rong; Li,Kang; Zhu,Kun; Dang,Chengxue; Yuan,Dawei

doi:10.3892/or.2020.7751

MicroRNA‑216a‑5p suppresses esophageal squamous cell carcinoma progression by targeting KIAA0101

Authors:
- Tuanhe Sun
- Qi An
- Rong Yan
- Kang Li
- Kun Zhu
- Chengxue Dang
- Dawei Yuan
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Affiliations: Department of Surgical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shannxi 710061, P.R. China, Department of Rheumatism and Immunology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shannxi 710061, P.R. China
Published online on: September 4, 2020 https://doi.org/10.3892/or.2020.7751
Pages: 1971-1984
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The KIAA0101 protein (also referred to as NS5ATP9 or Paf15) is overexpressed in esophageal squamous cell carcinoma (ESCC) and is associated with disease progression and poor patient survival, but how KIAA0101 expression is regulated remains unknown. The relationship between tumor miR‑216a‑5p expression and prognosis in patients with ESCC was revealed by survival analyses. Quantitative reverse‑transcriptase PCR and western blot analysis were used to evaluate miR‑216a‑5p and KIAA0101 expression in human ESCC tissues and cell lines. The targeting of KIAA0101 by miR‑216a‑5p was verified by dual‑luciferase reporter assays. The EC9706 and TE1 cell lines were transfected with miR‑216a‑5p mimics and inhibitor, or KIAA0101‑specific shRNA and KIAA0101‑expressing plasmids, in order to evaluate the effect of manipulating miR‑216a‑5p and KIAA0101 expression on ESCC cell proliferation, cell cycle progression, migration, and invasion. miR‑216a‑5p was lowly expressed and inversely correlated with KIAA0101 protein expression in ESCC tissues and cell lines. Lower miR‑216a‑5p expression was associated with worse prognosis in patients with ESCC. miR‑216a‑5p negatively regulated KIAA0101 expression by directly targeting the 3'‑untranslated region of the KIAA0101 mRNA. Overexpression of miR‑216a‑5p suppressed the proliferation, migration, and invasion of the ESCC cell lines, whereas inhibition of miR‑216a‑5p had the opposite effects. Meanwhile, KIAA0101 promoted ESCC migration and invasion, and its overexpression abolished the antitumor effects of miR‑216a‑5p mimics. As a tumor suppressor, miR‑216a‑5p targets KIAA0101 to inhibit the proliferation, migration, and invasion of ESCC. Therefore, the miR‑216a‑5p/KIAA0101 axis may be a potential target for ESCC treatment.

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1	Pennathur A, Gibson MK, Jobe BA and Luketich JD: Oesophageal carcinoma. Lancet. 381:400–412. 2013. View Article : Google Scholar : PubMed/NCBI
2	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
3	Lin Y, Totsuka Y, He Y, Kikuchi S, Qiao Y, Ueda J, Wei W, Inoue M and Tanaka H: Epidemiology of esophageal cancer in Japan and China. J Epidemiol. 23:233–242. 2013. View Article : Google Scholar : PubMed/NCBI
4	Talukdar F, di Pietro M, Secrier M, Moehler M, Goepfert K, Lima SSC, Pinto LFR, Hendricks D, Parker MI and Herceg Z: Molecular landscape of esophageal cancer: Implications for early detection and personalized therapy. Ann N Y Acad Sci. 1434:342–359. 2018. View Article : Google Scholar : PubMed/NCBI
5	Yu P, Huang B, Shen M, Lau C, Chan E, Michel J, Xiong Y, Payan DG and Luo Y: p15(PAF), a novel PCNA associated factor with increased expression in tumor tissues. Oncogene. 20:484–489. 2001. View Article : Google Scholar : PubMed/NCBI
6	Jain M, Zhang L, Patterson EE and Kebebew E: KIAA0101 is overexpressed, and promotes growth and invasion in adrenal cancer. PLoS One. 6:e268662011. View Article : Google Scholar : PubMed/NCBI
7	Cheng Y, Li K, Diao D, Zhu K, Shi L, Zhang H, Yuan D, Guo Q, Wu X, Liu D and Dang C: Expression of KIAA0101 protein is associated with poor survival of esophageal cancer patients and resistance to cisplatin treatment in vitro. Lab Invest. 93:1276–1287. 2013. View Article : Google Scholar : PubMed/NCBI
8	Zhang T, Guo J, Gu J, Chen K, Wang Z, Li H, Wang G and Wang J: KIAA0101 is a novel transcriptional target of FoxM1 and is involved in the regulation of hepatocellular carcinoma microvascular invasion by regulating epithelial-mesenchymal transition. J Cancer. 10:3501–3516. 2019. View Article : Google Scholar : PubMed/NCBI
9	Kong X, Gong S, Su L, Li C and Kong Y: Expression signatures and roles of MicroRNAs in human oesophageal adenocarcinomas. J Cell Mol Med. 22:123–130. 2018. View Article : Google Scholar : PubMed/NCBI
10	Feng Q, Zhang H, Yao D, Chen WD and Wang YD: Emerging role of non-coding RNAs in esophageal squamous cell carcinoma. Int J Mol Sci. 21:2582019. View Article : Google Scholar
11	Chen P, Quan J, Jin L, Lin C, Xu W, Xu J, Guan X, Chen Z, Ni L, Yang S, et al: MiR-216a-5p acts as an oncogene in renal cell carcinoma. Exp Ther Med. 15:4039–4046. 2018.PubMed/NCBI
12	Yonemori K, Seki N, Idichi T, Kurahara H, Osako Y, Koshizuka K, Arai T, Okato A, Kita Y, Arigami T, et al: The microRNA expression signature of pancreatic ductal adenocarcinoma by RNA sequencing: Anti-tumour functions of the microRNA-216 cluster. Oncotarget. 8:70097–70115. 2017. View Article : Google Scholar : PubMed/NCBI
13	Chai L and Yang G: MiR-216a-5p targets TCTN1 to inhibit cell proliferation and induce apoptosis in esophageal squamous cell carcinoma. Cell Mol Biol Lett. 24:462019. View Article : Google Scholar : PubMed/NCBI
14	Zhang Y, Lin P, Zou JY, Zou G, Wang WZ, Liu YL, Zhao HW and Fang AP: MiR-216a-5p act as a tumor suppressor, regulating the cell proliferation and metastasis by targeting PAK2 in breast cancer. Eur Rev Med Pharmacol Sci. 23:2469–2475. 2019.PubMed/NCBI
15	Ji Q, Xu X, Li L, Goodman SB, Bi W, Xu M, Xu Y, Fan Z, Maloney WJ, Ye Q and Wang Y: miR-216a inhibits osteosarcoma cell proliferation, invasion and metastasis by targeting CDK14. Cell Death Dis. 8:e31032017. View Article : Google Scholar : PubMed/NCBI
16	Wang D, Li Y, Zhang C, Li X and Yu J: MiR-216a-3p inhibits colorectal cancer cell proliferation through direct targeting COX-2 and ALOX5. J Cell Biochem. 119:1755–1766. 2018. View Article : Google Scholar : PubMed/NCBI
17	Xia H, Ooi LL and Hui KM: MicroRNA-216a/217-induced epithelial-mesenchymal transition targets PTEN and SMAD7 to promote drug resistance and recurrence of liver cancer. Hepatology. 58:629–641. 2013. View Article : Google Scholar : PubMed/NCBI
18	Wang RT, Xu M, Xu CX, Song ZG and Jin H: Decreased expression of miR216a contributes to non-small-cell lung cancer progression. Clin Cancer Res. 20:4705–4716. 2014. View Article : Google Scholar : PubMed/NCBI
19	Ajani JA, D'Amico TA, Bentrem DJ, Chao J, Corvera C, Das P, Denlinger CS, Enzinger PC, Fanta P, Farjah F, et al: Esophageal and esophagogastric junction cancers, version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 17:855–883. 2019. View Article : Google Scholar : PubMed/NCBI
20	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
21	Yuan D, Zhu K, Dang C, Zheng Y, Yan R, Shi L and Li K: NS5ATP9 mRNA levels in peripheral blood mononuclear cells predict prognosis in patients with gastric cancer. Med Oncol. 31:1062014. View Article : Google Scholar : PubMed/NCBI
22	Liang H, Fan JH and Qiao YL: Epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China. Cancer Biol Med. 14:33–41. 2017. View Article : Google Scholar : PubMed/NCBI
23	Warbrick E: A functional analysis of PCNA-binding peptides derived from protein sequence, interaction screening and rational design. Oncogene. 25:2850–2859. 2006. View Article : Google Scholar : PubMed/NCBI
24	Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N and Choudhary C: Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass. Nat Cell Biol. 14:1089–1098. 2012. View Article : Google Scholar : PubMed/NCBI
25	Emanuele MJ, Ciccia A, Elia AE and Elledge SJ: Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate. Proc Natl Acad Sci USA. 108:9845–9850. 2011. View Article : Google Scholar : PubMed/NCBI
26	Liu L, Chen X, Xie S, Zhang C, Qiu Z and Zhu F: Variant 1 of KIAA0101, overexpressed in hepatocellular carcinoma, prevents doxorubicin-induced apoptosis by inhibiting p53 activation. Hepatology. 56:1760–1769. 2012. View Article : Google Scholar : PubMed/NCBI
27	Hosokawa M, Takehara A, Matsuda K, Eguchi H, Ohigashi H, Ishikawa O, Shinomura Y, Imai K, Nakamura Y and Nakagawa H: Oncogenic role of KIAA0101 interacting with proliferating cell nuclear antigen in pancreatic cancer. Cancer Res. 67:2568–2576. 2007. View Article : Google Scholar : PubMed/NCBI
28	Kais Z, Barsky SH, Mathsyaraja H, Zha A, Ransburgh DJ, He G, Pilarski RT, Shapiro CL, Huang K and Parvin JD: KIAA0101 interacts with BRCA1 and regulates centrosome number. Mol Cancer Res. 9:1091–1099. 2011. View Article : Google Scholar : PubMed/NCBI
29	Severgnini M, Sherman J, Sehgal A, Jayaprakash NK, Aubin J, Wang G, Zhang L, Peng CG, Yucius K, Butler J and Fitzgerald K: A rapid two-step method for isolation of functional primary mouse hepatocytes: Cell characterization and asialoglycoprotein receptor based assay development. Cytotechnology. 64:187–195. 2012. View Article : Google Scholar : PubMed/NCBI
30	Zhu K, Diao D, Dang C, Shi L, Wang J, Yan R, Yuan D and Li K: Elevated KIAA0101 expression is a marker of recurrence in human gastric cancer. Cancer Sci. 104:353–359. 2013. View Article : Google Scholar : PubMed/NCBI
31	Li L and Ma H: MicroRNA-216a inhibits the growth and metastasis of oral squamous cell carcinoma by targeting eukaryotic translation initiation factor 4B. Mol Med Rep. 12:3156–3162. 2015. View Article : Google Scholar : PubMed/NCBI
32	Wang S, Chen X and Tang M: MicroRNA-216a inhibits pancreatic cancer by directly targeting Janus kinase 2. Oncol Rep. 32:2824–2830. 2014. View Article : Google Scholar : PubMed/NCBI
33	Fadejeva I, Olschewski H and Hrzenjak A: MicroRNAs as regulators of cisplatin-resistance in non-small cell lung carcinomas. Oncotarget. 8:115754–115773. 2017. View Article : Google Scholar : PubMed/NCBI
34	Zhang XX, Deng LH, Chen WW, Shi N, Jin T, Lin ZQ, Ma Y, Jiang K, Yang XN and Xia Q: Circulating microRNA 216 as a marker for the early identification of severe acute pancreatitis. Am J Med Sci. 353:178–186. 2017. View Article : Google Scholar : PubMed/NCBI
35	Link A, Becker V, Goel A, Wex T and Malfertheiner P: Feasibility of fecal microRNAs as novel biomarkers for pancreatic cancer. PLoS One. 7:e429332012. View Article : Google Scholar : PubMed/NCBI
36	Liu FY, Zhou SJ, Deng YL, Zhang ZY, Zhang EL, Wu ZB, Huang ZY and Chen XP: MiR-216b is involved in pathogenesis and progression of hepatocellular carcinoma through HBx-miR-216b-IGF2BP2 signaling pathway. Cell Death Dis. 6:e16702015. View Article : Google Scholar : PubMed/NCBI