Long non-coding RNA PCAT1 drives clear cell renal cell carcinoma by upregulating YAP via sponging miR-656 and miR-539.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common RCC subtype with high metastasis, poor prognosis and conventional chemotherapy resistance. Prostate cancer associated transcript 1 (PCAT1) is an important lncRNA that was reported to be involved in cell proliferation, migration and invasion of several types of cancer cells. However, its role in ccRCC is still undetermined. This study found that PCAT1 levels were elevated in ccRCC tumors as well as several ccRCC cells, and knockdown of PCAT1 with siRNA (si-PCAT1) alleviated cell proliferation, migration and invasion of Caki-2 and ACHN cells. With bioinformatics analysis, dual-luciferase reported assay, RNA pull-down assay and Spearman's correlation analysis, we demonstrated that PCAT1 acted as a sponge for miR-656 and miR-539. Moreover, we found dual competitive interaction of miR-656/539 with PCAT1 and yes-associated protein (YAP), resulting in the identification of PCAT1-miR-656/539-YAP axis in Caki-2 and ACHN cells. With CCK-8 assay and transwell assay, miR-656/539 inhibitor or YAP overexpression could alleviate the effects of si-PCAT1 on the proliferation, migration and invasion of Caki-2 and ACHN cells. Our data indicated that PCAT1 promotes proliferation, migration and invasion of ccRCC cells by upregulating YAP via sponging miR-656 and miR-539. Taken together, this study provided a novel therapeutic target for ccRCC treatment.

• Authors: Rui Wang, Bin Zheng, Hongyan Liu, Xiuxian Wan
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 19 Issue 10 Pg. 1122-1131 (05 2020) ISSN: 1551-4005 [Electronic] United States
• PMID: 32286142 (Publication Type: Journal Article)

Chemical References

• Cell Cycle Proteins
• MIRN539 microRNA, human
• MIRN656 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• Transcription Factors
• YY1AP1 protein, human
• long non-coding RNA PCAT1, human

Topics

• Animals
• Carcinoma, Renal Cell (metabolism, pathology)
• Case-Control Studies
• Cell Cycle Proteins (metabolism)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Female
• Gene Knockdown Techniques
• Humans
• Kidney Neoplasms (metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (metabolism)
• Middle Aged
• RNA, Long Noncoding (genetics, metabolism)
• Signal Transduction (genetics)
• Transcription Factors (metabolism)
• Transfection
• Tumor Burden (genetics)
• Up-Regulation (genetics)
• Xenograft Model Antitumor Assays