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RNF135 Promoter Methylation Is Associated With Immune Infiltration and Prognosis in Hepatocellular Carcinoma

Authors :
Xiao Wang
Mengke Chen
Xiong Liang
Yu Bai
Judeng Zeng
Xiaoyi Xu
Hao Li
Jing Wang
Keyu Fan
Guijun Zhao
Source :
Frontiers in Oncology, Vol 11 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

RING finger protein 135 has an important role in the occurrence of many cancers; however its regulation and function of RNF135 in hepatocellular carcinoma remains unknown. The promoter methylation status and mRNA expression of RNF135 was evaluated by methylation-specific PCR, semi-quantitative RT-PCR, and real-time quantitative PCR in HCC tissues and cell lines, and further analyzed from The Cancer Genome Atlas database. Wound healing assay, transwell migration, cell viability, and colony formation assay were performed to investigate the function of RNF135. GSEA analysis, TIMER database, and ESTIMATE algorithm were used to decipher the associated pathway and immune infiltration. The survival analysis was applied to assess the prognostic value of RNF135. RNF135 expression was downregulated in HCC tissues and 5 of 8 HCC cell lines, and was negatively correlated with its promoter hypermethylation. Demethylating regent decitabine restored RNF135 expression on the cellular level. Knockdown of RNF135 expression enhanced the migration of HCC cells, while RNF135 overexpression and decitabine treatment repressed cell migration. Bioinformatics analysis and immunohistochemistry revealed a positive relationship between RNF135 expression and six immune cell infiltrates (B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells). Survival analysis disclosed that RNF135 hypermethylation is independently associated with poor clinical outcomes in HCC. Decreased RNF135 expression driven by promoter hypermethylation frequently occurred in HCC and associated with prognosis of HCC. RNF135 functions as a tumor suppressor and is involved in tumor immune microenvironment in HCC.

Details

Language :
English
ISSN :
2234943X
Volume :
11
Database :
Directory of Open Access Journals
Journal :
Frontiers in Oncology
Publication Type :
Academic Journal
Accession number :
edsdoj.447278e35fc6463f9c3206f7e6dd57c4
Document Type :
article
Full Text :
https://doi.org/10.3389/fonc.2021.752511