N⁶-methyladenosine methyltransferase KIAA1429 elevates colorectal cancer aerobic glycolysis via HK2-dependent manner

Abstract

Emerging evidence has emphasized the critical roles played by N 6 -methyladenosine RNA (m 6 A) modification in colorectal carcinoma (CRC) initiation and progression. However, the roles and mechanism of m 6 A and KIAA1429 in CRC progression require further clarification. Here, our research aimed to investigate the functions of KIAA1429 in CRC tumorigenesis. Results indicated that KIAA1429 up-regulation closely correlated to the poor prognosis of CRC patients. Bio-functional assays demonstrated that KIAA1429 promoted the aerobic glycolysis, including glucose uptake, lactate production, ATP generation and extracellular acidification rate (ECAR). Mechanistically, KIAA1429 positively up-regulated HK2 level via increasing its mRNA stability by binding the m 6 A site of HK2 mRNA via m 6 A-independent manner. Collectively, our work indicates that KIAA1429 has the potential to promote CRC carcinogenesis by targeting HK2 via m 6 A-independent manner, providing insight into the critical roles of m 6 A in CRC.

YY1 transcription factor induces proliferation and aerobic glycolysis of neuroblastoma cells via LDHA regulation

“…GLUT1, a member of the GLUT family, the glucose transporter is an important protein that regulates intracellular glycolytic flux (29). Li et al (30) demonstrated that downregulation of HK-2-mediated glycolysis can inhibit the malignant progression of colorectal cancer. PDHK1 catalyzes glucose phosphorylation and inactivates PDH, the key enzyme for pyruvate to enter the citric acid cycle.…”

The biological function of m6A methyltransferase KIAA1429 and its role in human disease

“… Li et al (2022) studied the role of KIAA1429 in CRC. The results showed that KIAA1429 upregulation was closely related to poor prognosis of CRC patients.…”

Critical roles and clinical perspectives of RNA methylation in cancer

“…In vivo experiment on the BALB/c nude mice injected HCT116 cells with or without LINRIS knockdown observes that LINRIS knockdown suppresses the growth of CRC tumors and glycolysis mediated by IGF2BP2–MYC axis 355 . Emerging evidence indicates that the m 6 A methyltransferase KIAA1429 promotes aerobic glycolysis by upregulating HK2 expression 356 . Moreover, the m 6 A writer YTHDF2 degrades circ_0003215 to suppress signaling via the miR‐663b/discs large MAGUK scaffold protein 4 (DLG4)/G6PD axis and subsequently upregulate PPP and enhance the malignant phenotypes of CRC 357 .…”