RNF113A promotes the proliferation, migration and invasion, and is associated with a poor prognosis of esophageal squamous cell carcinoma

Wang,Lei; Hou,Zhichao; Hasim,Ayshamgul; Abuduerheman,Abulajiang; Zhang,Haiping; Niyaz,Madiniyat; Awut,Idiris; Upur,Halmurat; Sheyhidin,Ilyar

doi:10.3892/ijo.2018.4253

RNF113A promotes the proliferation, migration and invasion, and is associated with a poor prognosis of esophageal squamous cell carcinoma

Authors:
- Lei Wang
- Zhichao Hou
- Ayshamgul Hasim
- Abulajiang Abuduerheman
- Haiping Zhang
- Madiniyat Niyaz
- Idiris Awut
- Halmurat Upur
- Ilyar Sheyhidin
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Affiliations: Department of Thoracic Surgery, Τhe First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830054, P.R. China, Department of Pathology, Medical University of Xinjiang, Urumqi, Xinjiang Uygur Autonomous Region 830054, P.R. China, Clinical Medical Research Institute, Τhe First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830054, P.R. China, Department of Uyghur Medicine, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830054, P.R. China
Published online on: January 24, 2018 https://doi.org/10.3892/ijo.2018.4253
Pages: 861-871

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Abstract

Ring finger protein 113A (RNF113A) possesses a C3HC4 zinc finger domain and this domain is found in E3 ubiquitin ligase and is involved in tumorigenesis. To date, and at least to the best of our knowledge, there are no studies available which have investigated RNF113A in cancer. Thus, this study aimed to explore the role of RNF113A in the development of esophageal squamous cell carcinoma (ESCC). For this purpose, paraffin-embedded samples from 117 patients with ESCC were selected, as well as 41 pairs of fresh-frozen ESCC and adjacent normal tissue samples. RNF113A expression was examined by immunohistochemistry and reverse transcription-quantitative PCR (RT-qPCR). RNF113A was overexpressed or silenced in the EC9706 and Eca109 cells. The cells were examined for cell cycle progression, apoptosis, invasiveness and migration. Xenograft tumors were also created in mice using the Eca109 cells. Tumor differentiation (P=0.008) and T classification (P<0.001) were found to be significantly associated with RNF113A expression. No statistically significant association was observed between RNF113A expression and sex, age, histological type, tumor location and lymph node metastasis (N classification). Kaplan-Meier analysis revealed that the patients with ESCC with ahigh expression of RNF113A had a lower survival rate than those with a low expression (P=0.002). Multivariate analysis revealed that RNF113A expression (HR=2.406; 95% CI, 1.301-4.449, P=0.005) was independently associated with overall survival in patients with ESCC. The overexpression of RNF113A promoted proliferation, migration, and invasiveness of ESCC cell lines in vitro, and RNF113A silencing reversed these malignant behaviors. RNF113A knockdown inhibited tumor growth in vivo. Thus, these results indicate that RNF113A promotes the proliferation, migration and invasiveness of ESCC cell lines. RNF113A expression in ESCC is this associated with a poor prognosis of affected patients.

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1	Parkin DM, Pisani P and Ferlay J: Global cancer statistics. CA Cancer J Clin. 49:33–64. 311999. View Article : Google Scholar : PubMed/NCBI
2	Chen W, Zheng R, Zeng H, Zhang S and He J: Annual report on status of cancer in China, 2011. Chin J Cancer Res. 27:2–12. 2015. View Article : Google Scholar : PubMed/NCBI
3	Yang CS, Chen X and Tu S: Etiology and prevention of esophageal cancer. Gastrointest Tumors. 3:3–16. 2016. View Article : Google Scholar : PubMed/NCBI
4	Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
5	Arnold M, Soerjomataram I, Ferlay J and Forman D: Global incidence of oesophageal cancer by histological subtype in 2012. Gut. 64:381–387. 2015. View Article : Google Scholar
6	Ainiwaer J, Li DS and Zhang L: Investigation on prevalence of esophageal cancer during 2005–2008 in Yili of Xinjiang, China. Xinjiang Medical J. 41:112–114. 2011.
7	NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Esophageal and Esophagogastric Junction Cancers. (Version 2.2017). National Comprehensive Cancer Network; Fort Washington: 2017
8	Mukhopadhyay D and Riezman H: Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science. 315:201–205. 2007. View Article : Google Scholar : PubMed/NCBI
9	Sullivan JA, Shirasu K and Deng XW: The diverse roles of ubiquitin and the 26S proteasome in the life of plants. Nat Rev Genet. 4:948–958. 2003. View Article : Google Scholar : PubMed/NCBI
10	Xue Z, Wu X, Chen X, Liu Y, Wang X, Wu K, Nie Y and Fan D: Mesenchymal stem cells promote epithelial to mesenchymal transition and metastasis in gastric cancer though paracrine cues and close physical contact. J Cell Biochem. 116:618–627. 2015. View Article : Google Scholar
11	Díaz VM, Viñas-Castells R and García de Herreros A: Regulation of the protein stability of EMT transcription factors. Cell Adhes Migr. 8:418–428. 2014. View Article : Google Scholar
12	Corbett MA, Dudding-Byth T, Crock PA, Botta E, Christie LM, Nardo T, Caligiuri G, Hobson L, Boyle J, Mansour A, et al: A novel X-linked trichothiodystrophy associated with a nonsense mutation in RNF113A. J Med Genet. 52:269–274. 2015. View Article : Google Scholar : PubMed/NCBI
13	Frattini A, Faranda S, Bagnasco L, Patrosso C, Nulli P, Zucchi I and Vezzoni P: Identification of a new member (ZNF183) of the Ring finger gene family in Xq24-25. Gene. 192:291–298. 1997. View Article : Google Scholar : PubMed/NCBI
14	Korneta I, Magnus M and Bujnicki JM: Structural bioinformatics of the human spliceosomal proteome. Nucleic Acids Res. 40:7046–7065. 2012. View Article : Google Scholar : PubMed/NCBI
15	Carney TD, Struck AJ and Doe CQ: midlife crisis encodes a conserved zinc-finger protein required to maintain neuronal differentiation in Drosophila. Development. 140:4155–4164. 2013. View Article : Google Scholar : PubMed/NCBI
16	Bromberg KD, Kluger HM, Delaunay A, Abbas S, DiVito KA, Krajewski S and Ronai Z: Increased expression of the E3 ubiquitin ligase RNF5 is associated with decreased survival in breast cancer. Cancer Res. 67:8172–8179. 2007. View Article : Google Scholar : PubMed/NCBI
17	Chen C, Sun X, Guo P, Dong XY, Sethi P, Zhou W, Zhou Z, Petros J, Frierson HF Jr, Vessella RL, et al: Ubiquitin E3 ligase WWP1 as an oncogenic factor in human prostate cancer. Oncogene. 26:2386–2394. 2007. View Article : Google Scholar
18	Amsterdam A, Nissen RM, Sun Z, Swindell EC, Farrington S and Hopkins N: Identification of 315 genes essential for early zebrafish development. Proc Natl Acad Sci USA. 101:12792–12797. 2004. View Article : Google Scholar : PubMed/NCBI
19	Lee H, Alpi AF, Park MS, Rose A and Koo HS: C. elegans ring finger protein RNF-113 is involved in interstrand DNA crosslink repair and interacts with a RAD51C homolog. PLoS One. 8:e600712013. View Article : Google Scholar : PubMed/NCBI
20	Pellagatti A, Esoof N, Watkins F, Langford CF, Vetrie D, Campbell LJ, Fidler C, Cavenagh JD, Eagleton H, Gordon P, et al: Gene expression profiling in the myelodysplastic syndromes using cDNA microarray technology. Br J Haematol. 125:576–583. 2004. View Article : Google Scholar : PubMed/NCBI
21	Heath-Brown N: International Union Against Cancer. The Stateman's Yearbook 2016. Palgrave MacMillan; London: 2015
22	Ma JQ, Tuersun H, Jiao SJ, Zheng JH, Xiao JB and Hasim A: Functional role of NRF2 in cervical carcinogenesis. PLoS One. 10:e01338762015. View Article : Google Scholar : PubMed/NCBI
23	Sinicrope FA, Ruan SB, Cleary KR, Stephens LC, Lee JJ and Levin B: Bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res. 55:237–241. 1995.PubMed/NCBI
24	Zhu J, Li H, Ma J, Huang H, Qin J and Li Y: PTPN9 promotes cell proliferation and invasion in Eca109 cells and is negatively regulated by microRNA-126. Oncol Lett. 14:1419–1426. 2017. View Article : Google Scholar : PubMed/NCBI
25	Chen HX, Wang S, Wang Z, Zhang ZP and Shi SS: Overexpression of RUNX3 inhibits malignant behaviour of Eca109 cells in vitro and in vivo. Asian Pac J Cancer Prev. 15:1531–1537. 2014. View Article : Google Scholar
26	Li S, Wang F, Qu Y, Chen X, Gao M, Yang J, Zhang D, Zhang N, Li W and Liu H: HDAC2 regulates cell proliferation, cell cycle progression and cell apoptosis in esophageal squamous cell carcinoma EC9706 cells. Oncol Lett. 13:403–409. 2017. View Article : Google Scholar : PubMed/NCBI
27	Sun Z, Ji N, Bi M, Wang S, Liu X and Wang Z: PTEN gene is infrequently hypermethylated in human esophageal squamous cell carcinoma. Tumour Biol. 36:5849–5857. 2015. View Article : Google Scholar : PubMed/NCBI
28	Wang T, Xuan X, Pian L, Gao P, Hu H, Zheng Y, Zang W and Zhao G: Notch-1-mediated esophageal carcinoma EC-9706 cell invasion and metastasis by inducing epithelial-mesenchymal transition through Snail. Tumour Biol. 35:1193–1201. 2014. View Article : Google Scholar
29	Cory G: Scratch-wound assay. Methods Mol Biol. 769:25–30. 2011. View Article : Google Scholar : PubMed/NCBI
30	Jonkman JE, Cathcart JA, Xu F, Bartolini ME, Amon JE, Stevens KM and Colarusso P: An introduction to the wound healing assay using live-cell microscopy. Cell Adhes Migr. 8:440–451. 2014. View Article : Google Scholar
31	Sugiura T, Yamaguchi A and Miyamoto K: A cancer-associated RING finger protein, RNF43, is a ubiquitin ligase that interacts with a nuclear protein, HAP95. Exp Cell Res. 314:1519–1528. 2008. View Article : Google Scholar : PubMed/NCBI
32	Zhu J, Zhao C, Zhuang T, Jonsson P, Sinha I, Williams C, Strömblad S and Dahlman-Wright K: RING finger protein 31 promotes p53 degradation in breast cancer cells. Oncogene. 35:1955–1964. 2016. View Article : Google Scholar :
33	Horie K, Urano T, Ikeda K and Inoue S: Estrogen-responsive RING finger protein controls breast cancer growth. J Steroid Biochem Mol Biol. 85:101–104. 2003. View Article : Google Scholar : PubMed/NCBI
34	Oyanagi H, Takenaka K, Ishikawa S, Kawano Y, Adachi Y, Ueda K, Wada H and Tanaka F: Expression of LUN gene that encodes a novel RING finger protein is correlated with development and progression of non-small cell lung cancer. Lung Cancer. 46:21–28. 2004. View Article : Google Scholar : PubMed/NCBI
35	Zhang Y, Zhang Y, Yun H, Lai R and Su M: Correlation of STAT1 with apoptosis and cell-cycle markers in esophageal squamous cell carcinoma. PLoS One. 9:e1139282014. View Article : Google Scholar : PubMed/NCBI
36	Bozzuto G, Ruggieri P and Molinari A: Molecular aspects of tumor cell migration and invasion. Ann Ist Super Sanita. 46:66–80. 2010.PubMed/NCBI
37	Friedl P and Wolf K: Tumour-cell invasion and migration: Diversity and escape mechanisms. Nat Rev Cancer. 3:362–374. 2003. View Article : Google Scholar : PubMed/NCBI
38	Yonemori K, Seki N, Kurahara H, Osako Y, Idichi T, Arai T, Koshizuka K, Kita Y, Maemura K and Natsugoe S: ZFP36L2 promotes cancer cell aggressiveness and is regulated by antitumor microRNA-375 in pancreatic ductal adenocarcinoma. Cancer Sci. 108:124–135. 2017. View Article : Google Scholar :
39	Zhang Y and Yang WB: Down-regulation of tripartite motif protein 59 inhibits proliferation, migration and invasion in breast cancer cells. Biomed Pharmacother. 89:462–467. 2017. View Article : Google Scholar : PubMed/NCBI
40	Deng J, Liang H, Zhang R, Hou Y, Liu Y, Ying G, Pan Y and Hao X: Clinical and experimental role of ring finger protein 180 on lymph node metastasis and survival in gastric cancer. Br J Surg. 103:407–416. 2016. View Article : Google Scholar : PubMed/NCBI
41	Wang H, Wang Y, Qian L, Wang X, Gu H, Dong X, Huang S, Jin M, Ge H, Xu C, et al: RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy. Oncotarget. 7:51174–51183. 2016.PubMed/NCBI
42	Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, Nakamura T, Yabusaki H, Aoyama N, Kurita A, et al: A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 19:68–74. 2012. View Article : Google Scholar
43	Lazzari E and Meroni G: TRIM32 ubiquitin E3 ligase, one enzyme for several pathologies: From muscular dystrophy to tumours. Int J Biochem Cell Biol. 79:469–477. 2016. View Article : Google Scholar : PubMed/NCBI
44	Cai W and Yang H: The structure and regulation of Cullin 2 based E3 ubiquitin ligases and their biological functions. Cell Div. 11:72016. View Article : Google Scholar : PubMed/NCBI
45	Geng R, Tan X, Wu J, Pan Z, Yi M, Shi W, Liu R, Yao C, Wang G, Lin J, et al: RNF183 promotes proliferation and metastasis of colorectal cancer cells via activation of NF-κB-IL-8 axis. Cell Death Dis. 8:e29942017. View Article : Google Scholar
46	Liu ZY, Cao J, Zhang JT, Xu GL, Li XP, Wang FT, Ansari KH, Mohamed H and Fan YZ: Ring finger protein 125, as a potential highly aggressive and unfavorable prognostic biomarker, promotes the invasion and metastasis of human gallbladder cancers via activating the TGF-β1-SMAD3-ID1 signaling pathway. Oncotarget. 8:49897–49914. 2017.PubMed/NCBI