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KIAA1429 promotes cell proliferation by regulating MYC messenger RNA in clear cell renal cell carcinoma

ABSTRACT: KIAA1429 is an integral component of the m6A methyltransferase complex, essential for facilitating the interaction between the catalytic core components METTL3 and METTL14. However, the mechanisms by which KIAA1429 influences clear cell Renal cell carcinoma (ccRCC) remain incompletely elucidated. Analysis of the TCGA and GEO database confirmed that KIAA1429 was significantly upregulated in ccRCC samples, which correlated with poor survival. Additionally, qRT-PCR, Western Blot and IHC detection revealed significantly upregulated levels of KIAA1429 in ccRCC tissues. Moreover, multivariable Cox regression analysis showed that patients with ccRCC with high KIAA1429 expression had a poor clinical prognosis. Notably, silencing KIAA1429 significantly inhibited the proliferation, migration and invasion of ccRCC cells. Similarly, KIAA1429 knockdown also significantly inhibited the growth of ccRCC cells in nude mice. Mechanistically, KIAA1429 silencing significantly reduced the overall level of m6A in, the stability of MYC mRNA and the mRNA and protein expressions of MYC in ccRCC cells. Furthermore, RIP-qRT-PCR experiments showed that KIAA1429 could directly bind to MYC mRNA. MeRIP assay revealed that KIAA1429 knockdown resulted in a significant decrease in the m6A level of MYC mRNA in ccRCC cells. In conclusion, KIAA1429 regulates the proliferation, migration and invasion of ccRCC cells by stabilizing MYC mRNA in an m6A-dependent manner. Therefore, targeting the KIAA1429-MYC signalling pathway emerges as a potential strategy for the treatment of renal cell carcinoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE276431 | GEO | 2024/09/10

REPOSITORIES: GEO

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Genome-wide identification of transcripts associated with KIAA1429 by RIP-seq

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KIAA1429/VIRMA promotes breast cancer proliferation and migration by stabilizing m6A-modified HAS2 RNA expression in cytosol

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Expression data from Chinese renal cell carcinoma cells with FSTL1 knocked down

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Project description:Chronic hepatitis B virus (HBV) remains to be the most common risk factor of hepatocellular carcinoma (HCC). While work has primarily focussed on understanding the direct and indirect mechanisms of Hepatitis B virus X protein (HBx) mediated hepatocarcinogenesis, from genetic and epigenetic perspectives, its influence on RNA modification mediated onset of liver malignancies is less well understood. This study explored the role of HBV-encoded HBx in altering the m6A methylome profile and its implications on the pathogenesis of HCC. We established HBx expressing stable HCC cell lines, Huh7-HBx and HepG2-HBx, and explored the transcriptomic and epitranscriptomic profiles by RNA-seq and MeRIP-seq, respectively. Preliminary results suggest that HBx promotes liver cell proliferation, migration, survival and overall m6A methylation in HCC cells and is involved in modulating the extracellular matrix. We show that HBx mediates liver cell transformation by upregulating KIAA1429 methyltransferase. HBx also drives the expression and hypermethylation of the extracellular matrix protein HSPG2/Perlecan and promotes tumourigenesis. Our findings indicate a potential interaction between KIAA1429 and HSPG2, thus could be novel targets in combating HBx-driven HCC and warrants further investigation.

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