ZC3H15 promotes gastric cancer progression by targeting the FBXW7/c-Myc pathway

Zinc finger CCCH-type containing 15 (ZC3H15), a highly conserved eukaryotic protein, which was associated with several cellular processes and was ubiquitously expressed in various human tissues. Recent studies indicated that ZC3H15 was involved in tumorigenesis and may be a potential biomarker in he...

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Published inCell death discovery Vol. 8; no. 1; p. 32
Main Authors Hou, Jianbing, Huang, Pan, Lan, Chao, Geng, Shengjun, Xu, Minghao, Liu, Yudong, Chang, Hongbo, Wang, Zhongze, Gu, Hongyu, Wang, Yi, Yang, Guang, Cui, Hongjuan
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 21.01.2022
Springer Nature B.V
Nature Publishing Group
Subjects
631/67/1504/1829
692/699/67/1857
Acute myeloid leukemia
Apoptosis
Biochemistry
Biomedical and Life Sciences
c-Myc protein
Cdc4 protein
Cell Biology
Cell Cycle Analysis
Cell migration
Cell proliferation
Gastric cancer
Hepatocellular carcinoma
Life Sciences
Myc protein
Stem Cells
Transcription
Tumorigenesis
Zinc finger proteins
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Summary:Zinc finger CCCH-type containing 15 (ZC3H15), a highly conserved eukaryotic protein, which was associated with several cellular processes and was ubiquitously expressed in various human tissues. Recent studies indicated that ZC3H15 was involved in tumorigenesis and may be a potential biomarker in hepatocellular carcinoma (HCC) and acute myeloid leukemia (AML). However, the biological function and molecular mechanism of ZC3H15 in gastric cancer (GC) have not been studied. In this study, we revealed that ZC3H15 was highly expressed in GC and high ZC3H15 expression was closely linked to poor survival of patients with GC. We found that ZC3H15 promoted cell proliferation, migration, and invasion by increasing c-Myc expression. Next, we found that ZC3H15 could modulate c-Myc protein stability by suppressing the transcription of FBXW7, which was mainly responsible for c-Myc degradation. Moreover, silencing of FBXW7 in ZC3H15-knockdown GC cells could partly abrogate the effects induced by ZC3H15 downregulation. Taken together, our data unearth the important roles of ZC3H15 in GC development and suggest that ZC3H15 may be a potential target for the treatment of GC.
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ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-022-00815-x