Abstract
Colorectal cancer (CRC) is one of the most common malignancies globally. Increasing evidence indicates that circular RNAs (circRNAs) play a pivotal role in various cancers. The present study focused on exploring the role of a functionally unknown circRNA, hsa_circ_0062682 (circ_0062682), in CRC. By online analyses and experimental validations, we showed that circ_0062682 expression was aberrantly increased in CRC tissues compared with paired normal tissues. Increased expression of circ_0062682 in CRC notably correlated with a poor 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 D-3-phosphoglycerate dehydrogenase (PHGDH), a key oxidoreductase involved in serine biosynthesis, as a novel target of miR-940. Silencing miR-940 expression could mimic the inhibitory effect of circ_0062682 knockdown on CRC proliferation. The expression of PHGDH was downregulated in circ_0062682-depleted or miR-940 overexpressing CRC cells at both the mRNA and protein levels. Circ_0062682 knockdown suppressed CRC growth by decreasing PHGDH expression and serine production via miR-940. Taken together, these data demonstrate, for the first time, that 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.
Highlights
Colorectal cancer (CRC) is one of the most common malignancies, ranking third in terms of incidence and second in terms of mortality globally (Sung et al, 2021)
Imported serine and serine from the glycolytic branch can be converted to glycine, which is further utilized to promote nucleotide synthesis and GSH production
We reported for the first time that circ_0062682, as a stress-induced Circular RNA (circRNA), is able to promote serine synthesis and tumor growth by regulating the miR-940/phosphoglycerate dehydrogenase (PHGDH) axis
Summary
Colorectal cancer (CRC) is one of the most common malignancies, ranking third in terms of incidence and second in terms of mortality globally (Sung et al, 2021). Circular RNA (circRNA) is a new type of non-coding RNA (ncRNA) that forms a covalently closed loop without terminal 5′ caps and 3′ polyadenylated tails (Kristensen et al, 2019). Hsa_circ_0062682 Promotes CRC Proliferation closed circular structure, circRNAs are more stable and resistant to RNase R than linear transcripts, highlighting them as promising biomarkers (Chen, 2020). CircRNAs are functionally involved in mediating various cellular processes, including cell proliferation, differentiation and metabolism (Patop et al, 2019; Yin et al, 2019). The role of circRNAs in regulating the metabolic adaptation of cancer cells in a nutrientlimited microenvironment is unclear
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