Downregulation of RNF138 inhibits cellular proliferation, migration, invasion and EMT in glioma cells via suppression of the Erk signaling pathway Corrigendum in /10.3892/or.2022.8337

Wu,Haibin; Li,Xuetao; Feng,Ming; Yao,Lin; Deng,Zhitong; Zao,Guozheng; Zhou,Youxin; Chen,Sansong; Du,Ziwei

doi:10.3892/or.2018.6744

Downregulation of RNF138 inhibits cellular proliferation, migration, invasion and EMT in glioma cells via suppression of the Erk signaling pathway

Corrigendum in: /10.3892/or.2022.8337

Authors:
- Haibin Wu
- Xuetao Li
- Ming Feng
- Lin Yao
- Zhitong Deng
- Guozheng Zao
- Youxin Zhou
- Sansong Chen
- Ziwei Du
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Affiliations: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Neurosurgery, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China
Published online on: September 28, 2018 https://doi.org/10.3892/or.2018.6744
Pages: 3285-3296
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioma is the most common adult malignant primary brain tumor; however, the effect of chemotherapy is often limited by drug‑resistance and poor prognosis is common. Ring finger protein 138 (RNF138) belongs to the E3 ligase family, and has significantly higher expression level in glioma tissue than in noncancerous brain tissues. Epithelial-mesenchymal-transition (EMT) has a critical role in cancer invasion and metastasis, ultimately leading to increased cell motility and resistance to genotoxic agents. Extracellular‑signal regulated kinase (Erk) pathways promote the growth of glioma cells and enhance tumor invasion, with a role in the progression of EMT. However, the association between RNF138 and human glioma progression remains poorly understood. Relatively little is known about the association between RNF138, Erk, and EMT in glioma progression. In the current study, experiments were performed to explore the potential roles and mechanisms of RNF138 in glioblastoma in vitro and in vivo. Glioma cell line proliferation, migration and invasion were inhibited by knockdown of RNF138 in vitro. By lowering the RNF138 expression, cleaved caspase3 and E‑cadherin were upregulated, while phospho‑Erk1/2, vimentin, MMP2, HIF‑1α and VEGF were downregulated in U87 and U251 cells in vitro. In vivo findings revealed that the growth of U87 cell‑transplanted tumors in nude mice was inhibited in tumors with RNF138 knockdown. These findings suggested that downregulation of RNF138 inhibited glioma cell proliferation, migration, and invasion, and reversed EMT, potentially via Erk signaling pathway. Therefore, RNF138 may be a potential therapeutic target against glioma.

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1	Malzkorn B and Reifenberger G: Practical implications of integrated glioma classification according to the World Health Organization classification of tumors of the central nervous system 2016. Curr Opin Oncol. 28:494–501. 2016. View Article : Google Scholar : PubMed/NCBI
2	Winter SF, Loebel F and Dietrich J: Role of ketogenic metabolic therapy in malignant glioma: A systematic review. Crit Rev Oncol Hematol. 112:41–58. 2017. View Article : Google Scholar : PubMed/NCBI
3	Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C and Barnholtz-Sloan J: CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2007–2011. Neuro Oncol. 16 Suppl 4:iv1–iv63. 2014. View Article : Google Scholar : PubMed/NCBI
4	Tanaka S, Louis DN, Curry WT, Batchelor TT and Dietrich J: Diagnostic and therapeutic avenues for glioblastoma: No longer a dead end? Nat Rev Clin Oncol. 10:14–26. 2013. View Article : Google Scholar : PubMed/NCBI
5	Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, et al: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 10:459–466. 2009. View Article : Google Scholar : PubMed/NCBI
6	Carlsson SK, Brothers SP and Wahlestedt C: Emerging treatment strategies for glioblastoma multiforme. EMBO Mol Med. 6:1359–1370. 2014. View Article : Google Scholar : PubMed/NCBI
7	Liang J, Wang WF, Xie S, Zhang XL, Qi WF, Zhou XP, Hu JX, Shi Q and Yu RT: Expression of β-transducin repeat-containing E3 ubiquitin protein ligase in human glioma and its correlation with prognosis. Oncol Lett. 9:2651–2656. 2015. View Article : Google Scholar : PubMed/NCBI
8	Liu Y, Wang F, Liu Y, Yao Y, Lv X, Dong B, Li J, Ren S, Yao Y and Xu Y: RNF135, RING finger protein, promotes the proliferation of human glioblastoma cells in vivo and in vitro via the ERK pathway. Sci Rep. 6:206422016. View Article : Google Scholar : PubMed/NCBI
9	Xu L, Lu Y, Han D, Yao R, Wang H, Zhong S, Luo Y, Han R, Li K, Fu J, et al: Rnf138 deficiency promotes apoptosis of spermatogonia in juvenile male mice. Cell Death Dis. 8:e27952017. View Article : Google Scholar : PubMed/NCBI
10	Zhou YX, Chen SS, Wu TF, Ding DD, Chen XH, Chen JM, Su ZP, Li B, Chen GL, Xie XS, et al: A novel gene RNF138 expressed in human gliomas and its function in the glioma cell line U251. Anal Cell Pathol (Amst). 35:167–178. 2012. View Article : Google Scholar : PubMed/NCBI
11	Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI
12	Kang Y and Massagué J: Epithelial-mesenchymal transitions: Twist in development and metastasis. Cell. 118:277–279. 2004. View Article : Google Scholar : PubMed/NCBI
13	Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2:442–454. 2002. View Article : Google Scholar : PubMed/NCBI
14	Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI
15	Han MZ, Huang B, Chen AJ, Zhang X, Xu R, Wang J and Li XG: High expression of RAB43 predicts poor prognosis and is associated with epithelial-mesenchymal transition in gliomas. Oncol Rep. 37:903–912. 2017. View Article : Google Scholar : PubMed/NCBI
16	Zhang L, Zhang W, Li Y, Alvarez A, Li Z, Wang Y, Song L, Lv D, Nakano I, Hu B, et al: SHP-2-upregulated ZEB1 is important for PDGFRalpha-driven glioma epithelial-mesenchymal transition and invasion in mice and humans. Oncogene. 35:5641–5652. 2016. View Article : Google Scholar : PubMed/NCBI
17	Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, et al: The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 55:611–622. 2009. View Article : Google Scholar : PubMed/NCBI
18	Li X, Zhang G, Wang Y, Elgehama A, Sun Y, Li L, Gu Y, Guo W and Xu Q: Loss of periplakin expression is associated with the tumorigenesis of colorectal carcinoma. Biomed Pharmacother. 87:366–374. 2017. View Article : Google Scholar : PubMed/NCBI
19	Li Y, Hu Y, Liu C, Wang Q, Han X, Han Y, Xie XS, Chen XH, Li X, Siegel ER, et al: Human fibulin-3 protein variant expresses anti-cancer effects in the malignant glioma extracellular compartment in intracranial xenograft models. Oncotarget. 8:106311–106323. 2017.PubMed/NCBI
20	Clingerman KJ and Summers L: Validation of a body condition scoring system in rhesus macaques (Macaca mulatta): inter- and intrarater variability. J Am Assoc Lab Anim Sci. 51:31–36. 2012.PubMed/NCBI
21	Deng J, Wang L, Chen H, Hao J, Ni J, Chang L, Duan W, Graham P and Li Y: Targeting epithelial-mesenchymal transition and cancer stem cells for chemoresistant ovarian cancer. Oncotarget. 7:55771–55788. 2016. View Article : Google Scholar : PubMed/NCBI
22	Buonato JM and Lazzara MJ: ERK1/2 blockade prevents epithelial-mesenchymal transition in lung cancer cells and promotes their sensitivity to EGFR inhibition. Cancer Res. 74:309–319. 2014. View Article : Google Scholar : PubMed/NCBI
23	Ding C, Tang W, Fan X, Wang X, Wu H, Xu H, Xu W, Gao W and Wu G: Overexpression of PEAK1 contributes to epithelial-mesenchymal transition and tumor metastasis in lung cancer through modulating ERK1/2 and JAK2 signaling. Cell Death Dis. 9:8022018. View Article : Google Scholar : PubMed/NCBI
24	Brown JS and Jackson SP: Ubiquitylation, neddylation and the DNA damage response. Open Biol. 5:1500182015. View Article : Google Scholar : PubMed/NCBI
25	Han D, Liang J, Lu Y, Xu L, Miao S, Lu LY, Song W and Wang L: Ubiquitylation of Rad51d mediated by E3 ligase Rnf138 promotes the homologous recombination repair pathway. PLoS One. 11:e01554762016. View Article : Google Scholar : PubMed/NCBI
26	Yang B, Qin J, Nie Y, Li Y and Chen Q: Brain-derived neurotrophic factor propeptide inhibits proliferation and induces apoptosis in C6 glioma cells. Neuroreport. 28:726–730. 2017. View Article : Google Scholar : PubMed/NCBI
27	Wang XQ, Bai HM, Li ST, Sun H, Min LZ, Tao BB, Zhong J and Li B: Knockdown of HDAC1 expression suppresses invasion and induces apoptosis in glioma cells. Oncotarget. 8:48027–48040. 2017.PubMed/NCBI
28	Hou M, Cheng Z, Shen H, He S, Li Y, Pan Y, Feng C, Chen X, Zhang Y, Lin M, et al: High expression of CTHRC1 promotes EMT of epithelial ovarian cancer (EOC) and is associated with poor prognosis. Oncotarget. 6:35813–35829. 2015. View Article : Google Scholar : PubMed/NCBI
29	Jayachandran A, Dhungel B and Steel JC: Epithelial-to-me-senchymal plasticity of cancer stem cells: Therapeutic targets in hepatocellular carcinoma. J Hematol Oncol. 9:742016. View Article : Google Scholar : PubMed/NCBI
30	Krebs AM, Mitschke J, Losada Lasierra M, Schmalhofer O, Boerries M, Busch H, Boettcher M, Mougiakakos D, Reichardt W, Bronsert P, et al: The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol. 19:518–529. 2017. View Article : Google Scholar : PubMed/NCBI
31	Pietilä M, Ivaska J and Mani SA: Whom to blame for metastasis, the epithelial-mesenchymal transition or the tumor microenvironment? Cancer Lett. 380:359–368. 2016. View Article : Google Scholar : PubMed/NCBI
32	De Craene B and Berx G: Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 13:97–110. 2013. View Article : Google Scholar : PubMed/NCBI
33	Micalizzi DS, Farabaugh SM and Ford HL: Epithelial-me-senchymal transition in cancer: Parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia. 15:117–134. 2010. View Article : Google Scholar : PubMed/NCBI
34	Vivanco I and Sawyers CL: The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2:489–501. 2002. View Article : Google Scholar : PubMed/NCBI
35	Zeng Z, Leng T, Feng X, Sun H, Inoue K, Zhu L and Xiong ZG: Silencing TRPM7 in mouse cortical astrocytes impairs cell proliferation and migration via ERK and JNK signaling pathways. PLoS One. 10:e01199122015. View Article : Google Scholar : PubMed/NCBI
36	Heigener DF, Gandara DR and Reck M: Targeting of MEK in lung cancer therapeutics. Lancet Respir Med. 3:319–327. 2015. View Article : Google Scholar : PubMed/NCBI
37	Liu Z, Dai H, Jia G, Li Y, Liu X and Ren W: Insufficient radiofrequency ablation promotes human hepatoma SMMC7721 cell proliferation by stimulating vascular endothelial growth factor overexpression. Oncol Lett. 9:1893–1896. 2015. View Article : Google Scholar : PubMed/NCBI
38	Dong F, Tian H, Yan S, Li L, Dong X, Wang F, Li J, Li C, Cao Z, Liu X and Liu J: Dihydroartemisinin inhibits endothelial cell proliferation through the suppression of the ERK signaling pathway. Int J Mol Med. 35:1381–1387. 2015. View Article : Google Scholar : PubMed/NCBI
39	Zhang D, Lu C and Ai H: Rab5a is overexpressed in oral cancer and promotes invasion through ERK/MMP signaling. Mol Med Rep. 16:4569–4576. 2017. View Article : Google Scholar : PubMed/NCBI
40	Morishita Y, Ookawara S, Hirahara I, Muto S and Nagata D: HIF-1α mediates Hypoxia-induced epithelial-mesenchymal transition in peritoneal mesothelial cells. Ren Fail. 38:282–289. 2016. View Article : Google Scholar : PubMed/NCBI
41	Mori H, Yao Y, Learman BS, Kurozumi K, Ishida J, Ramakrishnan SK, Overmyer KA, Xue X, Cawthorn WP, Reid MA, et al: Induction of WNT11 by hypoxia and hypoxia-inducible factor-1α regulates cell proliferation, migration and invasion. Sci Rep. 6:215202016. View Article : Google Scholar : PubMed/NCBI
42	Park SY, Jang WJ, Yi EY, Jang JY, Jung Y, Jeong JW and Kim YJ: Melatonin suppresses tumor angiogenesis by inhibiting HIF-1alpha stabilization under hypoxia. J Pineal Res. 48:178–184. 2010. View Article : Google Scholar : PubMed/NCBI