Pseudogene TDGF1P3 regulates the proliferation and metastasis of colorectal cancer cells via the miR-338-3p–PKM2 axis

• Published in: Biochemical and biophysical research communications 2023-01, Vol.638, p.7-13
• Main Authors: Ni, Qianwen, An, Min, Luo, Shi, Li, Xiaocui, He, Guijun, Shen, Manru, Xu, Linfang, Huang, Jiying, Yan, Meizhu, Fan, Yu, Gao, Zhenjun
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal cancer; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Gene Expression Regulation, Neoplastic; Humans; Mice; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; miR-338-3p; Neoplasm Proteins - genetics; Pseudogene; Pseudogenes; Pyruvate kinase M2; Teratocarcinoma-derived growth factor 1 pseudogene 3
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.11.054

Research in the past decade has revealed significant roles of pseudogenes in colorectal cancer (CRC). Here, the role of teratocarcinoma-derived growth factor 1 pseudogene 3 (TDGF1P3) in regulating the proliferation and invasion of CRC cells was investigated; in addition, its downstream targets were analyzed, and the underlying mechanisms were elucidated. TDGF1P3 was determined to be upregulated in CRC cells and tissues. Silencing TDGF1P3 substantially repressed cell proliferation, migration, and invasion in vitro. Similarly, in vivo assays showed that TDGF1P3 knockdown attenuated tumor growth in nude mice. Mechanistic investigations revealed that TDGF1P3 directly bound to miR-338-3p, thereby preventing miR-338-3p from binding to its target mRNA pyruvate kinase M2 (PKM2). Functional rescue tests indicated that TDGF1P3 regulates CRC cell proliferation and invasion by restraining the miR-338-3p–PKM2 axis. Thus, these data illustrated that TDGF1P3 exerts its oncogenic activity by upregulating PKM2 via competitively binding miR-338-3p, which may be a therapeutic target for CRC. •TDGF1P3 was upregulated in CRC tissue samples and cell lines.•TDGF1P3 knockdown suppressed CRC cell proliferation and invasion in vitro and attenuated tumor growth in vivo.•TDGF1P3 knockdown downregulated PKM2 via miR-338-3p.•TDGF1P3 regulated CRC cell malignant behaviors via the miR-338-3p–PKM2 axis.