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. 2024 Dec 31;25(1):2306674.
doi: 10.1080/15384047.2024.2306674. Epub 2024 Feb 19.

M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells

Yu-Yan Wang  1 , Lian-Hua Ye  2 , An-Qi Zhao  3 , Wei-Ran Gao  4 , Ning Dai  4 , Yu Yin  5 , Xin Zhang  4
Affiliations

M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells

Yu-Yan Wang et al. Cancer Biol Ther. .

Abstract

DIRAS family GTPase 1 (DIRAS1) has been reported as a potential tumor suppressor in other human cancer. However, its expression pattern and role in cervical cancer remain unknown. Knockdown of DIRAS1 significantly promoted the proliferation, growth, migration, and invasion of C33A and SiHa cells cultured in vitro. Overexpression of DIRAS1 significantly inhibited the viability and motility of C33A and SiHa cells. Compared with normal cervical tissues, DIRAS1 mRNA levels were significantly lower in cervical cancer tissues. DIRAS1 protein expression was also significantly reduced in cervical cancer tissues compared with para-cancerous tissues. In addition, DIRAS1 expression level in tumor tissues was significantly negatively correlated with the pathological grades of cervical cancer patients. DNA methylation inhibitor (5-Azacytidine) and histone deacetylation inhibitor (SAHA) resulted in a significant increase in DIRAS1 mRNA levels in C33A and SiHa cells, but did not affect DIRAS1 protein levels. FTO inhibitor (FB23-2) significantly down-regulated intracellular DIRAS1 mRNA levels, but significantly up-regulated DIRAS1 protein levels. Moreover, the down-regulation of METTL3 and METTL14 expression significantly inhibited DIRAS1 protein expression, whereas the down-regulation of FTO and ALKBH5 expression significantly increased DIRAS1 protein expression. In conclusion, DIRAS1 exerts a significant anti-oncogenic function and its expression is significantly downregulated in cervical cancer cells. The m6A modification may be a key mechanism to regulate DIRAS1 mRNA stability and protein translation efficiency in cervical cancer.

Keywords: Cervical cancer; DIRAS1; epigenetic regulation; m6A.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Knockdown of DIRAS1 significantly promotes proliferation, growth and motility of C33A and SiHa cells.
Figure 2.
Figure 2.
DIRAS1 overexpression significantly inhibits the proliferation, growth and motility of C33A and SiHa cells.
Figure 3.
Figure 3.
Altered expression pattern of DIRAS1 in cervical cancer tissues.
Figure 4.
Figure 4.
The mechanisms of epigenetic regulation to regulate DIRAS1.
Figure 5.
Figure 5.
M6A modification promotes DIRAS1 translation.
See this image and copyright information in PMC

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