MiR-765 Functions as a Tumor Suppressor and Lipid Eliminator in Clear Cell Renal Cell Carcinoma by Downregulating PLP2

Abstract

Background: Lipid accumulation has been highlighted in cancer development and progression, but the exact mechanism remains unclear in renal cell cancer (RCC). MicroRNAs (miRNAs) have been confirmed to participate in pathological processes of cancers, including tumor occurrence or inhibition. However, the role and mechanism of miR-765 have not been elucidated in clear cell renal cell cancer (ccRCC). Methods: Using the Cancer Genome Atlas (TCGA) database and qRT-PCR, we investigated differences in miR-765 and PLP2 expression, as well as their clinical relevance. To investigate the function of miR-765 and PLP2 in ccRCC, we performed in vitro and in vivo experiment to explore the biological functions in ccRCC. Findings: In this study, we showed miR-765 was upregulated in plasma of ccRCC patients after tumor resection. Consistently, ccRCC tissues had low expression of miR-765 when compared with corresponding noncancerous tissues. Overexpression of miR-765 suppressed cell proliferation and metastasis in vitro and in vivo. Mechanistic studies demonstrated that proteolipid protein 2 (PLP2) was a direct target gene of miR-765. PLP2 was highly expressed in ccRCC tissues and high PLP2 had positive correlation with higher tumor stage, grade and poor prognosis. PLP2 expression was negatively correlated with the miR-765 level in patient samples. We further showed that PLP2 restrained cell metastasis, proliferation and lipid elimination of miR-765 in renal cancer cells. Interpretation: Our findings suggest that miR-765 may be a tumor suppressor and lipid eliminator in clear cell renal cell carcinoma by targeting PLP2. Funding Statement: This work was funded the grants from the National Natural Scientific Foundation of China (Grant NO. 81672528, 81672524, 31741032). Declaration of Interests: The authors declare no conflicts of this manuscript. Ethics Approval Statement: Informed consent was told and obtained from patients, the procedures of experiment and study were approved by the Institutional Review board of Xiamen University. All animal experiments were performed in accordance with animal protocols approved by the Institutional Animal Use and Care Committee of Xiamen University.