YTHDF1 promotes the proliferation, migration, and invasion of prostate cancer cells by regulating TRIM44

Li, Weijian; Chen, Gaohuang; Feng, Zhenyu; Zhu, Baoyi; Zhou, Lingjun; Zhang, Yuying; Mai, Junyan; Jiang, Chonghe; Zeng, Jing

doi:10.1007/s13258-021-01175-z

Cited by 17 publications

(17 citation statements)

References 31 publications

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“…Overexpression of YTHN6-methyladenosine RNA binding protein 1 (YTHDF1), an N6-methyladenosine modification (m6A) reader, rescues the DSB DNA damage response 49 . A previous study demonstrated that TRIM44 is transcriptionally upregulated by YTHDF1 50 . In the DDR, whether the DSB-induced abundance of TRIM44 is dependent on YTHFF or other m6A enzymes requires further investigation.…”

Section: Discussionmentioning

confidence: 93%

TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA

Zhang¹,

Cao²,

Shi³

et al. 2022

Int. J. Biol. Sci.

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Tripartite motif-containing 44 (TRIM44) has recently been implicated in various pathological processes in numerous cancers, including lung adenocarcinoma (LUAD); however, its functional roles in chemoresistance are poorly understood. Herein, TRIM44 knockdown sensitized LUAD cells to cisplatin and enhanced cisplatin-induced apoptosis. Microarray analysis indicated that the “ Role of BRCA1 in DNA damage ” and the BRCA1 gene expression were positively regulated by TRIM44, which was further verified by immunofluorescence, qRT-PCR, and Western blotting. BRCA1 depletion effectively abolished TRIM44-modulated cisplatin resistance and regulation of homologous recombination (HR) repair. Interestingly, TRIM44 interacted with FLNA, an upstream regulator of BRCA1 as specified by STRING V 11.5, and facilitated its stability and deubiquitination. FLNA was also found to be required for the functions of TRIM44 in drug resistance. Using animal models, overexpression of TRIM44 was shown to confer resistance to cisplatin in a BRCA1- and FLNA-dependent manner. TRIM44 expression levels in tissues from cisplatin-resistant LUAD patients were significantly higher than those in tissues from cisplatin-sensitive LUAD patients. Collectively, our study results demonstrate that the TRIM44/FLNA/BRCA1 axis is involved in cisplatin chemoresistance, providing potential therapeutic targets for LUAD patients with cisplatin resistance.

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Section: Discussionmentioning

confidence: 93%

TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA

Zhang¹,

Cao²,

Shi³

et al. 2022

Int. J. Biol. Sci.

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“…The YTHDF family genes ( YTHDF1 , YTHDF2 , and YTHDF3 ) can recognize bases undergoing m6A methylation, as well as bases participating in downstream translation, mRNA degradation, and mRNA exit rate acceleration [ 60 ]. Previous studies have demonstrated that PC samples expressed higher levels of YTHDF1 and YTHDF2 mRNA compared to healthy tissue [ 61 , 62 ]. Upregulation of YTHDF1 and YTHDF2 promotes PC cell proliferation, invasion, and migration [ 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that PC samples expressed higher levels of YTHDF1 and YTHDF2 mRNA compared to healthy tissue [ 61 , 62 ]. Upregulation of YTHDF1 and YTHDF2 promotes PC cell proliferation, invasion, and migration [ 61 , 62 ]. In particular, YTHDF2 modulated PC phenotypes by regulating the expression of its significantly positively correlated gene, tripartite motif-containing 44 ( TRIM44 ) [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

“…Upregulation of YTHDF1 and YTHDF2 promotes PC cell proliferation, invasion, and migration [ 61 , 62 ]. In particular, YTHDF2 modulated PC phenotypes by regulating the expression of its significantly positively correlated gene, tripartite motif-containing 44 ( TRIM44 ) [ 61 ]. YTHDF2 may exert this action by binding to m6A modification sites on tumor suppressor genes, such as LHPP and NKX3-1 .…”

Section: Discussionmentioning

confidence: 99%

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Unveiling the m6A Methylation Regulator Links between Prostate Cancer and Periodontitis by Transcriptomic Analysis

et al. 2022

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Objective. To identify the N6-methyladenosine (m6A) methylation regulator genes linking prostate adenocarcinoma (PRAD) and periodontitis (PD). Materials and Methods. PD and TCGA-PRAD GEO datasets were downloaded and analyzed through differential expression analysis to determine the differentially expressed genes (DEGs) deregulated in both conditions. Twenty-three m6A RNA methylation-related genes were downloaded in total. The m6A-related genes that overlapped between PRAD and PD were identified as crosstalk genes. Survival analysis was performed on these genes to determine their prognostic values in the overall survival outcomes of prostate cancer. The KEGG pathways were the most significantly enriched by m6A-related crosstalk genes. We also performed lasso regression analysis and univariate survival analysis to identify the most important m6A-related crosstalk genes, and a protein-protein interaction (PPI) network was built from these genes. Results. Twenty-three m6A methylation-related regulator genes were differentially expressed and deregulated in PRAD and PD. Among these, seven (i.e., ALKBH5, FMR1, IGFBP3, RBM15B, YTHDF1, YTHDF2, and ZC3H13) were identified as m6A-related cross-talk genes. Survival analysis showed that only the FMR1 gene was a prognostic indicator for PRAD. All other genes had no significant influence on the overall survival of patients with PRAD. Lasso regression analysis and univariate survival analysis identified four m6A-related cross-talk genes (i.e., ALKBH5, IGFBP3, RBM15B, and FMR1) that influenced risk levels. A PPI network was constructed from these genes, and 183 genes from this network were significantly enriched in pathogenic Escherichia coli infection, p53 signaling pathway, nucleocytoplasmic transport, and ubiquitin-mediated proteolysis. Conclusion. Seven m6A methylation-related genes (ALKBH5, FMR1, IGFBP3, RBM15B, YTHDF1, YTHDF2, and ZC3H13) were identified as cross-talk genes between prostate cancer and PD.

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“… Prostate cancer TRIM44 Upregulated YTHDF1 promoted PCa cell proliferation, migration, and invasion by regulating TRIM44. Moreover, the prognosis of patients with PCa with high YTHDF1 was relatively poor [ 56 ]. Esophageal carcinoma / Upregulated Expression of YTHDF1 was associated with multiple clinical features in ESCA patients and involved in multiple ceRNA network [ 59 ].…”

Section: The Molecular Mechanism Of Ythdf1 In Cancersmentioning

confidence: 99%

The potential role of m6A reader YTHDF1 as diagnostic biomarker and the signaling pathways in tumorigenesis and metastasis in pan-cancer

Zhu

Yang

et al. 2023

Cell Death Discov.

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Abstractm6A is an important RNA methylation in progression of various human cancers. As the m6A reader protein, YTHDF1 is reported to accelerate m6A-modified mRNAs translation in cytoplasm. It is highly expressed in various human cancers and contributes to the progression and metastasis of cancers. YTHDF1 was closely associated with poor prognosis and also used as a molecular marker for clinical diagnosis or therapy in human cancers. It has been reported to promote chemoresistance to Adriamycin, Cisplatin and Olaparib by increasing mRNA stability of its target molecule. Moreover, it contributes to CSC-like characteristic of tumor cells and inducing the antitumor immune microenvironment. Here, we reviewed the clinical diagnostic and prognostic values of YTHDF1, as well as the molecular mechanisms of YTHDF1 in progression and metastasis of human cancers.

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YTHDF1 promotes the proliferation, migration, and invasion of prostate cancer cells by regulating TRIM44

Cited by 17 publications

References 31 publications

TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA

TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA

Unveiling the m6A Methylation Regulator Links between Prostate Cancer and Periodontitis by Transcriptomic Analysis

The potential role of m6A reader YTHDF1 as diagnostic biomarker and the signaling pathways in tumorigenesis and metastasis in pan-cancer

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