Protein tyrosine phosphatase PTPRJ is negatively regulated by microRNA‐328

Abstract

Expression of PTPRJ, which is a ubiquitous receptor-type protein tyrosine phosphatase, is significantly reduced in a vast majority of human epithelial cancers and cancer cell lines (i.e. colon, lung, thyroid, mammary and pancreatic tumours). A possible role for microRNAs (miRNAs) in the negative regulation of PTPRJ expression has never been investigated. In this study, we show that overexpression of microRNA-328 (miR-328) decreases PTPRJ expression in HeLa and SKBr3 cells. Further investigations demonstrate that miR-328 acts directly on the 3¢UTR of PTPRJ, resulting in reduced mRNA levels. Luciferase assay and site-specific mutagenesis were used to identify a functional miRNA response element in the 3¢UTR of PTPRJ. Expression of miR-328 significantly enhances cell proliferation in HeLa and SKBr3 cells, similar to the effects of downregulation of PTPRJ with small interfering RNA. Additionally, in HeLa cells, the proliferative effect of miR-328 was not observed when PTPRJ was silenced with small interfering RNA; conversely, restoration of PTPRJ expression in miR-328-overexpressing cells abolished the proliferative activity of miR-328. In conclusion, we report the identification of miR-328 as an important player in the regulation of PTPRJ expression, and we propose that the interaction of miR-328 with PTPRJ is responsible for miR-328-dependent increase of epithelial cell proliferation.

microRNA-328 is a favorable prognostic marker in human glioma via suppressing invasive and proliferative phenotypes of malignant cells

“…Expression of PTPRJ, a ubiquitous receptor-type protein tyrosine phosphatase, has been reported to be decreased in a vast majority of human epithelial cancers and cancer cell lines, such as thyroid cancer, lung cancer, mammary cancer, pancreatic cancer and colon cancer. Paduano et al [26] showed that overexpression of miR-328 could decrease PTPRJ expression and enhance cell proliferation of HeLa and SKBr3 cells. Boissonneault et al [27] indicated that miR-328 recognized specific binding sites in the 3 -UTR of BACE1 mRNA and exerted regulatory effects on BACE1 protein expression in cultured neuronal cells.…”

An overview of microRNAs

“…It should be noted that these non-canonical pathways appear to be rare events. For example, miR-328 predominantly functions as a canonical miRNA within the RISC complex, directing translational repression of target mRNAs[93-97]. …”

Early molecular and behavioral response to lipopolysaccharide in the WAG/Rij rat model of absence epilepsy and depressive-like behavior, involves interplay between AMPK, AKT/mTOR pathways and neuroinflammatory cytokine release

“…One microgram of RNA was subjected to the reaction of reverse-transcription using the high capacity RNA-to-cDNA Kit (Applied Biosystems), following the manufacturer's instructions. Five hundred nanolitres of cDNAs were amplified by real-time PCR with Power SYBR green PCR master mix (Applied Biosystems) and 5 pmol of primers in a total volume of 25 lL, as previously described (Paduano et al, 2013).…”