OB-RGRP regulates the phosphorylation of JAK2 and STAT3 in primary rat adipocytes

Abstract

This study aimed to explore the role of obestatin R gene-related protein (OB-RGRP) in autocrine signal transduction of adipocytes. Primary rat adipocytes were isolated and verified by microscopic observation and oil red O staining. OB-RGRP expression vector and OB-RGRP siRNA (si-OB-RGRP) were constructed and transfected into adipocytes. Adipocytes were then divided into five groups: (1) Control; (2) Vector (empty expression vector); (3) OB-RGRP (OB-RGRP expression vector); (4) si-OB-RGRP NC (si-OB-RGRP negative control); (5) si-OB-RGRP. mRNA and protein levels of OB-RGRP, JAK2, phosphorylated JAK2 (p-JAK2), STAT3 and phosphorylated STAT3 (p-STAT3) were examined using RT-PCR and western blot, respectively. Results showed that mRNA and protein levels of OB-RGRP in the Vector and si-OB-RGRP NC groups were similar to those in the Control group. Their levels in the si-OB-RGRP and OB-RGRP groups were significantly down-regulated and up-regulated (p < .05), respectively, in comparison with the control cells. There was no significant difference in the mRNA and protein levels of JAK2 and STAT3 among various groups. Moreover, the si-OB-RGRP NC and Vector groups induced similar ratios of p-JAK2 to JAK2 (p-JAK2/JAK2) and p-STAT3 to STAT3 (p-STAT3/STAT3) to the Control group. However, these two ratios in the si-OB-RGRP and OB-RGRP groups were significantly reduced and elevated (p < .05), respectively, in comparison with the Control group. These results suggested that OB-RGRP overexpression enhanced the levels of p-JAK2 and p-STAT3 while OB-RGRP silencing lowered their levels. In conclusion, OB-RGRP regulated the phosphorylation of JAK2 and STAT3 in primary rat adipocytes. ARTICLE HISTORY

Leptin Receptor Overlapping Transcript (LEPROT) Is Associated with the Tumor Microenvironment and a Prognostic Predictor in Pan-Cancer

“…In cancer cells, the molecular signaling processes were always aberrantly up/downregulated and/or functionally modified ( Li et al, 2019 ) ( Yang et al, 2020a ; Barrett and Puré, 2020 ). As a result of conflicting reports on the impact of LEPROT on downstream signaling and cancer progression, and the lack of investigation on it, a bioinformatic analysis on LEPROT among multiple cancer types was, therefore, conducted for a broader understanding of the roles of LEPROT in cancers.…”

“…Leptin exerts its biological action majorly through binding to and activating the leptin receptors (LEPR) ( Garofalo and Surmacz, 2006 ; Ghasemi et al, 2019 ), and the gene encoding LEPR overlapping transcript (LEPROT), which is shown to negatively regulate leptin signaling by reducing expressions of LEPR on the cell membrane, is considered as an anticancer factor in cancer progression. However, a more recent study paradoxically reported that LEPROT could activate the JAK/STAT signaling ( Li et al, 2019 ), which may theoretically facilitate cancer development ( Mullen and Gonzalez-Perez, 2016 ). Therefore, the role of LEPROT in tumors may not be limited to the previous cognition that it only serves as a negative regulator of leptin signaling.…”

Single-Nucleotide Polymorphisms in LEP and LEPR Associated With Breast Cancer Risk: Results From a Multicenter Case–Control Study in Chinese Females

“…Previous studies indicated that LEPROT could negatively regulate the cell surface expression of LEPR and the silencing LEPROT expression in the mouse hypothalamic arcuate nucleus prevented the development of high-fat-diet-induced obesity ( 19 ). In contrast, LEPROT was found to activate the JAK/STAT pathway and may facilitate cancer development ( 20 ). A recent study identified an aberrant expression of LEPROT in 78.9% cancers compared with corresponding normal tissues ( 21 ).…”

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“…In cancer cells, the molecular signaling processes were always aberrantly up/downregulated and/or functionally modified (Li et al, 2019) (Yang et al, 2020a;Barrett and Puré, 2020). As a result of conflicting reports on the impact of LEPROT on downstream signaling and cancer progression, and the lack of investigation on it, a bioinformatic analysis on LEPROT among multiple cancer types was, therefore, conducted for a broader understanding of the roles of LEPROT in cancers.…”