Tumor suppressor PLZF regulated by lncRNA ANRIL suppresses proliferation and epithelial mesenchymal transformation of gastric cancer cells Corrigendum in /10.3892/or.2023.8624

Wang,Jun‑Bin; Jin,Yan; Wu,Peng; Liu,Yang; Zhao,Wen‑Jing; Chen,Jin‑Fei; De,Wei; Yang,Fen

doi:10.3892/or.2018.6866

Tumor suppressor PLZF regulated by lncRNA ANRIL suppresses proliferation and epithelial mesenchymal transformation of gastric cancer cells

Corrigendum in: /10.3892/or.2023.8624

Authors:
- Jun‑Bin Wang
- Yan Jin
- Peng Wu
- Yang Liu
- Wen‑Jing Zhao
- Jin‑Fei Chen
- Wei De
- Fen Yang
View Affiliations

Affiliations: Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China, Department of Oncology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu 223300, P.R. China, Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China, Department of Clinical Pharmacy, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Published online on: November 12, 2018 https://doi.org/10.3892/or.2018.6866
Pages: 1007-1018

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Promyelocytic leukemia zinc finger (PLZF) plays important roles in tumorigenic and developmental processes of various types of cancers. However, the expression of PLZF in gastric cancer (GC) has not been reported. The aim of the present study was to investigate the expression level and potential status of PLZF in GC as well as its possible mechanism. In the present study, we found that PLZF was downregulated in the majority of GC cell lines and tumor tissues and that alteration of PLZF expression was closely correlated with a malignant phenotype, epithelial‑mesenchymal transformation and overall survival. Evaluation of in vitro proliferation, colony information, migration and invasion indicated that PLZF gene transduction induced a less malignant phenotype, which was also confirmed through in vivo studies performed in athymic nude mice. Furthermore, we assessed the expression levels of the lncRNA ANRIL in GC and found that it was negatively associated with the level of PLZF and that ANRIL indirectly methylated PLZF to suppress its expression via binding with polycomb repressive complex 2. When GC cells were treated with the methylation inhibitor 5‑Aza‑2'‑deoxycytidine, the expression of PLZF increased, which further confirmed that PLZF was methylated. These results indicated that constitutive ANRIL activation was a possible cause of the lack of PLZF expression in GC cells. Coupled deregulation of PLZF and ANRIL may account for most of the alterations described in GC, and PLZF may become a potential target of GC therapy.

View Figures

View References

1	Ball HJ, Melnick A, Shaknovich R, Kohanski RA and Licht JD: The promyelocytic leukemia zinc finger (PLZF) protein binds DNA in a high molecular weight complex associated with cdc2 kinase. Nucleic Acids Res. 27:4106–4113. 1999. View Article : Google Scholar : PubMed/NCBI
2	Suliman BA, Xu D and Williams BR: The promyelocytic leukemia zinc finger protein: Two decades of molecular oncology. Front Oncol. 2:742012. View Article : Google Scholar : PubMed/NCBI
3	Choi WI, Kim MY, Jeon BN, Koh DI, Yun CO, Li Y, Lee CE, Oh J, Kim K and Hur MW: Role of promyelocytic leukemia zinc finger (PLZF) in cell proliferation and cyclin-dependent kinase inhibitor 1A (p21WAF/CDKN1A) gene repression. J Biol Chem. 289:18625–18640. 2014. View Article : Google Scholar : PubMed/NCBI
4	Felicetti F, Errico MC, Bottero L, Segnalini P, Stoppacciaro A, Biffoni M, Felli N, Mattia G, Petrini M, Colombo MP, et al: The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res. 68:2745–2754. 2008. View Article : Google Scholar : PubMed/NCBI
5	Vincent A, Omura N, Hong SM, Jaffe A, Eshleman J and Goggins M: Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma. Clin Cancer Res. 17:4341–4354. 2011. View Article : Google Scholar : PubMed/NCBI
6	Matsuzawa K, Izawa S, Ohkura T, Ohkura H, Ishiguro K, Yoshida A, Takiyama Y, Haneda M, Shigemasa C, Yamamoto K, et al: Implication of intracellular localization of transcriptional repressor PLZF in thyroid neoplasms. BMC Endocr Disord. 14:522014. View Article : Google Scholar : PubMed/NCBI
7	Hsieh CL, Botta G, Gao S, Li T, Van Allen EM, Treacy DJ, Cai C, He HH, Sweeney CJ, Brown M, et al: PLZF, a tumor suppressor genetically lost in metastatic castration-resistant prostate cancer, is a mediator of resistance to androgen deprivation therapy. Cancer Res. 75:1944–1948. 2015. View Article : Google Scholar : PubMed/NCBI
8	Hui AW, Lau HW, Cao CY, Zhou JW, Lai PB and Tsui SK: Downregulation of PLZF in human hepatocellular carcinoma and its clinical significance. Oncol Rep. 33:397–402. 2015. View Article : Google Scholar : PubMed/NCBI
9	Xiao GQ, Li F, Findeis-Hosey J, Hyrien O, Unger PD, Xiao L, Dunne R, Kim ES, Yang Q, McMahon L, et al: Down-regulation of cytoplasmic PLZF correlates with high tumor grade and tumor aggression in non-small cell lung carcinoma. Hum Pathol. 46:1607–1615. 2015. View Article : Google Scholar : PubMed/NCBI
10	Jin Y, Nenseth HZ and Saatcioglu F: Role of PLZF as a tumor suppressor in prostate cancer. Oncotarget. 8:71317–71324. 2017. View Article : Google Scholar : PubMed/NCBI
11	Shen H, Zhan M, Zhang Y, Huang S, Xu S, Huang X, He M, Yao Y, Man M and Wang J: PLZF inhibits proliferation and metastasis of gallbladder cancer by regulating IFIT2. Cell Death Dis. 9:712018. View Article : Google Scholar : PubMed/NCBI
12	Jones C, St-Jean S, Fréchette I, Bergeron D, Rivard N and Boudreau F: Identification of a novel promyelocytic leukemia zinc-finger isoform required for colorectal cancer cell growth and survival. Int J Cancer. 133:58–66. 2013. View Article : Google Scholar : PubMed/NCBI
13	Fatica A and Bozzoni I: Long non-coding RNAs: New players in cell differentiation and development. Nat Rev Genet. 15:7–21. 2014. View Article : Google Scholar : PubMed/NCBI
14	Yap KL, Li S, Muñoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, Gil J, Walsh MJ and Zhou MM: Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell. 38:662–674. 2010. View Article : Google Scholar : PubMed/NCBI
15	Pasmant E, Laurendeau I, Héron D, Vidaud M, Vidaud D and Bièche I: Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: Identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Res. 67:3963–3969. 2007. View Article : Google Scholar : PubMed/NCBI
16	Chen S, Zhang JQ, Chen JZ, Chen HX, Qiu FN, Yan ML, Chen YL, Peng CH, Tian YF and Wang YD: The over expression of long non-coding RNA ANRIL promotes epithelial-mesenchymal transition by activating the ATM-E2F1 signaling pathway in pancreatic cancer: An in vivo and in vitro study. Int J Biol Macromol. 102:718–728. 2017. View Article : Google Scholar : PubMed/NCBI
17	Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, Kitagawa M and Xiong Y: Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15^INK4B tumor suppressor gene. Oncogene. 30:1956–1962. 2011. View Article : Google Scholar : PubMed/NCBI
18	Wang J, Hevi S, Kurash JK, Lei H, Gay F, Bajko J, Su H, Sun W, Chang H, Xu G, et al: The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat Genet. 41:125–129. 2009. View Article : Google Scholar : PubMed/NCBI
19	Liu X, Li C, Zhang R, Xiao W, Niu X, Ye X, Li Z, Guo Y, Tan J and Li Y: The EZH2- H3K27me3-DNMT1 complex orchestrates epigenetic silencing of the wwc1 gene, a Hippo/YAP pathway upstream effector, in breast cancer epithelial cells. Cell Signal. 51:243–256. 2018. View Article : Google Scholar : PubMed/NCBI
20	Long HK, King HW, Patient RK, Odom DT and Klose RJ: Protection of CpG islands from DNA methylation is DNA-encoded and evolutionarily conserved. Nucleic Acids Res. 44:6693–6706. 2016. View Article : Google Scholar : PubMed/NCBI
21	Nawaz I, Qiu X, Wu H, Li Y, Fan Y, Hu LF, Zhou Q and Ernberg I: Development of a multiplex methylation specific PCR suitable for (early) detection of non-small cell lung cancer. Epigenetics. 9:1138–1148. 2014. 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^−ΔΔ^C^T method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
23	Chen JF, Wu P, Xia R, Yang J, Huo XY, Gu DY, Tang CJ, De W and Yang F: STAT3-induced lncRNA HAGLROS overexpression contributes to the malignant progression of gastric cancer cells via mTOR signal-mediated inhibition of autophagy. Mol Cancer. 17:62018. View Article : Google Scholar : PubMed/NCBI
24	Yang F, Deng R, Qian XJ, Chang SH, Wu XQ, Qin J, Feng GK, Ding K and Zhu XF: Feedback loops blockade potentiates apoptosis induction and antitumor activity of a novel AKT inhibitor DC120 in human liver cancer. Cell Death Dis. 5:e11142014. View Article : Google Scholar : PubMed/NCBI
25	Marchese FP and Huarte M: Long non-coding RNAs and chromatin modifiers: Their place in the epigenetic code. Epigenetics. 9:21–26. 2014. View Article : Google Scholar : PubMed/NCBI
26	Cech TR and Steitz JA: The noncoding RNA revolution-trashing old rules to forge new ones. Cell. 157:77–94. 2014. View Article : Google Scholar : PubMed/NCBI
27	Huang MD, Chen WM, Qi FZ, Xia R, Sun M, Xu TP, Yin L, Zhang EB, De W and Shu YQ: Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell apoptosis by epigenetic silencing of KLF2. J Hematol Oncol. 8:502015. View Article : Google Scholar : PubMed/NCBI
28	Colquhoun A, Arnold M, Ferlay J, Goodman KJ, Forman D and Soerjomataram I: Global patterns of cardia and non-cardia gastric cancer incidence in 2012. Gut. 64:1881–1888. 2015. View Article : Google Scholar : PubMed/NCBI
29	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
30	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
31	Chia NY, Deng N, Das K, Huang D, Hu L, Zhu Y, Lim KH, Lee MH, Wu J, Sam XX, et al: Regulatory crosstalk between lineage-survival oncogenes KLF5GATA4GATA6 cooperatively promotes gastric cancer development. Gut. 64:707–719. 2015. View Article : Google Scholar : PubMed/NCBI
32	Thiem S, Eissmann MF, Elzer J, Jonas A, Putoczki TL, Poh A, Nguyen P, Preaudet A, Flanagan D, Vincan E, et al: Stomach-specific activation of oncogenic KRAS and STAT3-dependent inflammation cooperatively promote gastric tumorigenesis in a preclinical model. Cancer Res. 76:2277–2287. 2016. View Article : Google Scholar : PubMed/NCBI
33	Wang K, Liang Q, Li X, Tsoi H, Zhang J, Wang H, Go MY, Chiu PW, Ng EK, Sung JJ and Yu J: MDGA2 is a novel tumour suppressor cooperating with DMAP1 in gastric cancer and is associated with disease outcome. Gut. 65:1619–1631. 2016. View Article : Google Scholar : PubMed/NCBI
34	Wang X, Wang L, Guo S, Bao Y, Ma Y, Yan F, Xu K, Xu Z, Jin L, Lu D, et al: Hypermethylation reduces expression of tumor-suppressor PLZF and regulates proliferation and apoptosis in non-small-cell lung cancers. FASEB J. 27:4194–4203. 2013. View Article : Google Scholar : PubMed/NCBI
35	Felicetti F, Bottero L, Felli N, Mattia G, Labbaye C, Alvino E, Peschle C, Colombo MP and Carè A: Role of PLZF in melanoma progression. Oncogene. 23:4567–4576. 2004. View Article : Google Scholar : PubMed/NCBI
36	Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, et al: Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA. 106:11667–11672. 2009. View Article : Google Scholar : PubMed/NCBI
37	Nguyen CT, Gonzales FA and Jones PA: Altered chromatin structure associated with methylation-induced gene silencing in cancer cells: Correlation of accessibility, methylation, MeCP2 binding and acetylation. Nucleic Acids Res. 29:4598–4606. 2001. View Article : Google Scholar : PubMed/NCBI
38	Ombrato L and Malanchi I: The EMT universe: Space between cancer cell dissemination and metastasis initiation. Crit Rev Oncog. 19:349–361. 2014. View Article : Google Scholar : PubMed/NCBI