Cancer Manag Res.2022 Mar 17;14:1165-1177.doi: 10.2147/CMAR.S335749. eCollection 2022.

GPR27 Regulates Hepatocellular Carcinoma Progression via MAPK/ERK Pathway

Hongxv Wang #  1 Danyu Du #  2 Jianwen Huang #  3 Shuai Wang  2 Xv He  3 Shengtao Yuan  2 Jing Xiao  1 Affiliations

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Purpose: Orphan GPCRs (GPRs) play important roles in the malignant progression of cancer and have the potential to develop into anti-tumor drug targets. However, the biological processes and molecular mechanisms of GPR27 have not been properly assessed in cancer. Our objective was to reveal the effect of GPR27 on the progression of hepatocellular carcinoma (HCC).

Methods: GPR27 levels were detected in HCC cell lines using quantitative reverse transcriptase-polymerase chain reaction and Western blot analysis. Next, the changes of phenotypes after GPR27 knockdown or overexpression were evaluated using in vitro methods. Finally, the mechanism of GPR27 in HCC was tested using RNA-seq and in vivo mouse xenograft model.

Results: In the present study, we reported that suppression of GPR27 expression inhibited proliferation, colony formation, cell viability, and induced cell S phase arrest of HCC cells, whereas GPR27 overexpression led to the opposite outcomes. Moreover, suppression of GPR27 expression resulted in blocking MAPK/ERK signal pathway which indicated the inhibition of HCC cells proliferation. Further study in vivo confirmed that GPR27 can affect the proliferation of HCC cells through the MAPK/ERK pathway.

Conclusion: Taken together, the findings of the present study uncover biological functions of GPR27 in HCC cells, and delineate preliminary molecular mechanisms of GPR27 in modulating HCC development and progression.

Keywords: GPR27; MAPK/ERK pathway; hepatocellular carcinoma; proliferation.