Neoplasma Vol.70, No.5, p. 659–669, 2023
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| Title: TRIM11 regulated by m6A modification promotes the progression of cervical cancer by PHLPP1 ubiquitination |
| Author: Pu Zhang, Yi Tang, Jing Zhao, Jing Yang, Yan Chen, Yingping Gong, Shengjun Meng, Chuqiang Shu |
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Abstract: Cervical cancer (CC) is a common cancer in women and a serious threat to women’s lives. TRIM11 has been confirmed as a carcinogen in multiple cancers. Here, we will excavate the detailed mechanism of TRIM11 in CC. CC cell lines and nude mice were experimental subjects in this study. The abundance of genes and proteins was detected using qRT-PCR, western blot, and IHC. Cell proliferation, migration, and invasion were determined by CCK-8 assay, wound healing assay, and Transwell, respectively. The interactions among METTL14, TRIM11, and PHLPP1 were confirmed using RIP and co-IP, respectively. The stability of TRIM11 mRNA was examined by qRT-PCR with actinomycin D treatment. The m6A level of TRIM11 was detected by MeRIP assay. Results showed that TRIM11 levels were elevated in CC cells. TRIM11 depletion attenuated the proliferation, migration, and invasion of Hela and SiHa cells. Additionally, TRIM11 was modified with m6A, which was mediated by METTL14, and the stability of TRIM11 mRNA was enhanced by IGF2BP1 depending on the level of m6A modification. TRIM11 ubiquitinated PHLPP1 and led to reduced PHLPP1 expression at the protein level. PHLPP1 could further result in the dephosphorylation of AKT and inhibit AKT signaling. PHLPP1 knockdown neutralized TRIM11 silencing-mediated repression of malignant phenotypes of CC cells. TRIM11 mediated by the METTL14-IGF2BP1 axis promotes the AKT pathway to accelerate CC progression by mediating the ubiquitination of PHLPP, which might provide novel therapeutic targets for CC treatment.
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| Keywords: m6A modification; IGF2BP1; PHLPP1; TRIM11; ubiquitination; CC |
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Published online: 06-Dec-2023
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| Year: 2023, Volume: 70, Issue: 5 |
Page From: 659, Page To: 669 |
doi:10.4149/neo_2023_230104N7
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