Long noncoding RNA PENG upregulates PDZK1 expression by sponging miR-15b to suppress clear cell renal cell carcinoma cell proliferation.

Abstract

PDZK1 downregulation was reported to independently predict poor prognosis of clear cell renal cell carcinoma (ccRCC) patients and induce ccRCC development and progression. However, the underlying mechanism of PDZK1 downregulation remains unknown. Competing endogenous RNA (ceRNA) networks are emerging as new players in gene regulation and are associated with cancer development. ceRNAs regulate other RNA transcripts by competing for shared miRNAs. To investigate the role and mechanism of ceRNAs in PDZK1 downregulation and the development of ccRCC, we searched databases for miRNAs and lncRNAs that regulate PDZK1 expression in ccRCC tissues and assessed their effects in ccRCC. We found that miR-15b was expressed at higher levels in ccRCC tissues, and its upregulation was clinically associated with lower PDZK1 level, larger tumor size and shorter survival time of ccRCC patients. Conversely, a novel lncRNA (lncPENG) was expressed at a lower level in ccRCC tissues, and its downregulation was associated with the same effects as upregulation of miR-15b. Downregulation of miR-15b and upregulation of lncPENG resulted in a significant increase in PDZK1 level and inhibition of proliferation in vitro and in vivo. Mechanistically, lncPENG directly bound to miR-15b and effectively functioned as a sponge for miR-15b to modulate the expression of PDZK1. Thus, lncPENG may function as a ceRNA to attenuate miR-15b-dependent PDZK1 downregulation and inhibit cell proliferation, suggesting that it may be clinically valuable as a therapeutic target and a prognostic biomarker of ccRCC.

• Authors: Yijun Qi, Yuanzhen Ma, Zhiqiang Peng, Lei Wang, Lanxin Li, Yilan Tang, Junqi He, Junfang Zheng
• Journal: Oncogene (Oncogene) Vol. 39 Issue 22 Pg. 4404-4420 (05 2020) ISSN: 1476-5594 [Electronic] England
• PMID: 32341409 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• MIRN15 microRNA, human
• Membrane Proteins
• MicroRNAs
• Neoplasm Proteins
• PDZK1 protein, human
• RNA, Long Noncoding
• RNA, Neoplasm

Topics

• Animals
• Base Sequence
• Biomarkers, Tumor
• Carcinoma, Renal Cell (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Genes, Reporter
• Heterografts
• Humans
• In Situ Hybridization, Fluorescence
• Kidney Neoplasms (genetics, metabolism, pathology)
• Membrane Proteins (biosynthesis, genetics)
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Neoplasm Proteins (biosynthesis, genetics)
• Prognosis
• RNA, Long Noncoding (genetics)
• RNA, Neoplasm (antagonists & inhibitors, genetics, metabolism)
• Random Allocation
• Sequence Analysis, RNA
• Tumor Stem Cell Assay
• Up-Regulation