MBD1/HDAC3-miR-5701-FGFR2 axis promotes the development of gastric cancer

Gastric cancer (GC) remains one of the leading causes of cancer-related deaths worldwide due to the lack of specific biomarkers for the early diagnosis and universal accepted therapy for advanced GC. Lower levels of miR-5701 were found in the GC tissue from the online sequencing data and confirmed i...

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Veröffentlicht in:Aging (Albany, NY.) NY.), 2022-07, Vol.14 (14), p.5878-5894
Hauptverfasser: Zhao, Changan, Miao, Jiyu, Sun, Ruifang, Liang, Rui, Chen, Wenhu, Gao, Yi, Wang, Xiaofei, Han, Shuiping, Zhao, Wenbao, Lei, Ting, Huang, Chen
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Sprache:eng
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Zusammenfassung:Gastric cancer (GC) remains one of the leading causes of cancer-related deaths worldwide due to the lack of specific biomarkers for the early diagnosis and universal accepted therapy for advanced GC. Lower levels of miR-5701 were found in the GC tissue from the online sequencing data and confirmed in the GC tissues and GC cell lines. Overexpression of miR-5701 inhibited the proliferation and migration of GC cells and promoted the apoptosis of these cells. Bioinformatics analyses and luciferase assay showed that miR-5701 targeted FGFR2, which acted as an oncogene in GC. Nude mice with GC cells overexpressing miR-5701 exhibited smaller tumor sizes and less lung metastases. The miR-5701 expression was directly, transcriptionally inhibited by MBD1 together with HDAC3 by binding together to form a complex. Knocked down MBD1 or HDAC3 increased the miR-5701 expression. These results indicated the potential use of exogenously administered miR-5701 or agents that elevated endogenous miR-5701 to inhibit GC, improving the prognosis of patients with GC.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.204190