Overexpression of antisense long non‑coding RNA ZNF710‑AS1‑202 promotes cell proliferation and inhibits apoptosis of clear cell renal cell carcinoma via regulation of ZNF710 expression

Mol Med Rep. 2020 Jun;21(6):2502-2512. doi: 10.3892/mmr.2020.11032. Epub 2020 Mar 20.

Abstract

Antisense long non-coding RNAs (AS lncRNAs) have been increasingly recognized as important regulators of gene expression and have been found to play crucial roles in the development and progression of tumors. The present study explored the roles of AS lncRNA ZNF710‑AS1‑202 in clear cell renal cell carcinoma (ccRCC). The expression levels of ZNF710‑AS1‑202 were detected in 46 human ccRCC tissues and 34 healthy adjacent renal tissues. The associations between the levels of ZNF710‑AS1‑202 expression and the clinicopathological features of the patients were evaluated by the χ2 test. Gain‑ and loss‑of‑function experiments were performed to analyze the role of ZNF710‑AS1‑202 in ccRCC cell proliferation and survival in vitro. Reverse transcription‑quantitative PCR and/or western blotting were employed to detect ZNF710‑AS1‑202, zinc finger protein 710 (ZNF710) and cyclin B1 expression. The Cell Counting Kit‑8 and colony formation assays, as well as flow cytometry, were used to detect cell proliferation or apoptosis. The subcellular localization of ZNF710‑AS1‑202 was analyzed by RNA fluorescence in situ hybridization. The results revealed that ZNF710‑AS1‑202 was downregulated in human ccRCC tissues and was associated with the pathological grade, tumor size, local invasion and TNM stage, but not with lymph node metastasis or distant metastasis. However, ZNF710‑AS1‑202 overexpression promoted the proliferation of RCC cells and inhibited apoptosis. Opposite results were observed when ZNF710‑AS1‑202 was knocked down by small interfering RNA. Furthermore, ZNF710‑AS1‑202, which was mainly expressed in the cytoplasm of RCC cells, regulated ZNF710 mRNA and protein expression in opposing manners. In conclusion, the present study revealed that ZNF710‑AS1‑202 and ZNF710 may serve as promising therapeutic targets for ccRCC.

Keywords: clear cell renal cell carcinoma; antisense long non-coding rna; ZnF710-aS-202; proliferation; apoptosis.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / drug effects*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism*
  • Male
  • Middle Aged
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / pharmacology*
  • RNA, Messenger
  • RNA, Small Interfering / metabolism
  • Transcriptome

Substances

  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Small Interfering