Hsa_Circ_0062682 Promotes Serine Metabolism and Tumor Growth in Colorectal Cancer by Regulating the miR-940/PHGDH Axis

Background: Colorectal cancer (CRC) is one of the most common malignancy globally. Increasing evidences indicate that circular RNAs (circRNAs) play a pivotal role in various cancers. Methods: Differential circRNAs were determined by edgeR package. The expression of circ_0062682, miR-940 and PHGDH were analyzed by qRT-PCR. We used in vitro proliferation assays and in vivo xenograft model to evaluate the tumorigenic features of CRC cells. Abundance of serine were measured by liquid chromatography mass spectrometry assay. Findings: Increased expression of circ_0062682 in CRC notably correlated with a poorly prognosis and advanced tumor stage. Functional experiments showed that circ_0062682 knockdown reduced CRC growth both in vitro and in vivo. Mechanistically, we revealed that circ_0062682 could sponge miR-940 and identified that PHGDH, a key oxidoreductase involving in serine biosynthesis, as a novel target of miR-940. The expression of PHGDH was downregulated in circ_0062682–depleted or miR-940 overexpressing CRC cells at both mRNA and protein levels. Interpretation: Circ_0062682 promotes serine metabolism and tumor growth in CRC by regulating the miR-940/PHGDH axis, suggesting circ_0062682 as a potential novel therapeutic target for CRC. Funding: This study was partially supported by grants from the National Natural Science Foundation of China (81972220 and 82002964), Medical Key Professionals Program of Jiangsu Province (ZDRCB2016017), Wuxi Medical Innovation Team (CXTP003), and Medical Leading Talents of Wuxi Taihu Lake Talent Plan. Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics Approval Statement: Our study was approved by the Research Ethics Committee of Affiliated Hospital of Jiangnan University.