Small RNA-induced INTS6 gene up-regulation suppresses castration-resistant prostate cancer cells by regulating β-catenin signaling.

Abstract	Small RNAs play an important role in gene regulatory networks. The gene suppressive effect of small RNAs was previously the dominant focus of studies, but during the recent decade, small RNA-induced gene activation has been reported and has become a notable gene manipulation technique. In this study, a putative tumor suppressor, INTS6, was activated by introducing a promoter-targeted small RNA (dsRNA-915) into castration-resistant prostate cancer (CRPC) cells. Unique dynamics associated with the gene upregulation phenomenon was observed. Following gene activation, cell proliferation and motility were suppressed in vitro. Downregulation of Wnt/β-catenin signaling was observed during the activation period, and the impairment of β-catenin degradation reversed the tumor suppressor effects of INTS6. These results suggest the potential application of small activating RNAs in targeted gene therapy for CRPC.
Authors	Hong Chen, Hai-Xiang Shen, Yi-Wei Lin, Ye-Qing Mao, Ben Liu, Li-Ping Xie
Journal	Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 17 Issue 13 Pg. 1602-1613 ( 2018) ISSN: 1551-4005 [Electronic] United States
PMID	29895194 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	INTS6 protein, human RNA, Double-Stranded RNA-Binding Proteins Ribosomal Proteins Tumor Suppressor Proteins beta Catenin
Topics	Aged Base Sequence Cell Cycle Checkpoints Cell Line, Tumor Cell Movement Cell Survival (genetics) Clone Cells Down-Regulation (genetics) Epigenesis, Genetic Epithelial Cells (metabolism, pathology) Gene Expression Regulation, Neoplastic Humans Male Promoter Regions, Genetic (genetics) Prostatic Neoplasms, Castration-Resistant (genetics, pathology) RNA, Double-Stranded (metabolism) RNA-Binding Proteins Ribosomal Proteins (genetics, metabolism) Time Factors Transcriptional Activation Tumor Suppressor Proteins (genetics, metabolism) Up-Regulation (genetics) Wnt Signaling Pathway beta Catenin (metabolism)

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