Dataset Information

GPR12 Inhibits Apoptosis in Epithelial Ovarian Cancer via the Activation of ERK1/2 Signaling.

ABSTRACT: Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies in women worldwide. G protein-coupled receptor 12 (GPR12) is a member of G protein-coupled receptors (GPCRs) and plays an important role in the regulation of cell proliferation and survival. However, its role in EOC is underappreciated. In this study, we found that GPR12 is highly expressed in the EOC tissues and can be an ideal biomarker to predict the prognosis of patients with EOC. GPR12 knockdown obviously inhibits the proliferation of EOC cells by inducing cellular apoptosis in vitro and in vivo. Meanwhile, bioinformatic analysis showed that the inhibitory effect of GPR12 knockdown on the cell viability is closely related with Extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, which has been confirmed by the fact that the activity of ERK1/2 pathway has been significantly blocked in the GPR12 knockdown cells. LM22B-10, ERK1/2 pathway activator, could reverse the inhibited proliferation caused by GPR12 knockdown in the EOC cells. Our findings suggest that GPR12 is involved in the EOC process and is a potential therapeutic target for EOC.

SUBMITTER: Wang L

PROVIDER: S-EPMC9316591 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

GPR12 Inhibits Apoptosis in Epithelial Ovarian Cancer <i>via</i> the Activation of ERK1/2 Signaling.

Wang Lu L Yang Da D Zhang Yao Y Jiao Yisheng Y

Frontiers in oncology 20220712

Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies in women worldwide. G protein-coupled receptor 12 (GPR12) is a member of G protein-coupled receptors (GPCRs) and plays an important role in the regulation of cell proliferation and survival. However, its role in EOC is underappreciated. In this study, we found that GPR12 is highly expressed in the EOC tissues and can be an ideal biomarker to predict the prognosis of patients with EOC. GPR12 knockdown obviously i ...[more]

PMID: 35903681

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Project description:Circular RNA ABCB10 (circ‑ABCB10) modulates cellular functions and microRNA (miR)‑1271 in epithelial ovarian cancer (EOC). The present study aimed to investigate the interaction between circ‑ABCB10 and miR‑1271 in regulating EOC cellular function and the calpain small subunit 1 (Capn4)/Wnt/β‑catenin signaling pathway. circ‑ABCB10 and miR‑1271 expression levels were detected in EOC cells (OVCAR3, UWB1.289, SKOV3 and CAOV3) and normal ovarian epithelial cells (IOSE80) via reverse‑transcription quantitative PCR. SKOV3 cells were transfected with control short hairpin (sh)RNA plasmids, control inhibitor, circ‑ABCB10 shRNA plasmids and miR‑1271 inhibitor. UWB1.289 cells were transfected with control overexpression plasmids, control mimic, circ‑ABCB10 overexpression plasmids and miR‑1271 mimic. Subsequently, cell proliferation, apoptosis, invasion and the Capn4/Wnt/β‑catenin signaling pathway were assessed. In addition, a luciferase activity assay was performed. circ‑ABCB10 expression was significantly increased in OVCAR3, SKOV3 and CAOV3 cells compared with IOSE80 cells, but was not significantly altered in UWB1.289 cells. miR‑1271 expression was significantly decreased in OVCAR3, UWB1.289, SKOV3 and CAOV3 cells compared with IOSE80 cells. In both SKOV3 and UWB1.289 cells, circ‑ABCB10 negatively regulated miR‑1271, whereas miR‑1271 did not affect circ‑ABCB10. Furthermore, circ‑ABCB10 enhanced cell proliferation, invasion and the Capn4/Wnt/β‑catenin signaling pathway, but inhibited cell apoptosis, whereas miR‑1271 suppressed cell proliferation, invasion and the Capn4/Wnt/β‑catenin signaling pathway, but facilitated cell apoptosis. Moreover, miR‑1271 attenuated the proproliferative, proinvasive and antiapoptotic effects of circ‑ABCB10, and reversed the positive regulation of circ‑ABCB10 on the Capn4/Wnt/β‑catenin signaling pathway. Besides, the luciferase activity assay indicated that circ‑ABCB10 directly bound to miR‑1271. In conclusion, the present study indicated that circ‑ABCB10 promoted cell proliferation and invasion, and suppressed apoptosis by regulating the miR‑1271‑mediated Capn4/Wnt/β‑catenin signaling pathway in EOC.

Dataset Information

GPR12 Inhibits Apoptosis in Epithelial Ovarian Cancer via the Activation of ERK1/2 Signaling.

Publications

GPR12 Inhibits Apoptosis in Epithelial Ovarian Cancer <i>via</i> the Activation of ERK1/2 Signaling.

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