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

Jianbing Hou; Pan Huang; Chao Lan; Shengjun Geng; Minghao Xu; Yudong Liu; Hongbo Chang; Zhongze Wang; Hongyu Gu; Yi Wang; Guang Yang; Hongjuan Cui

doi:10.1038/s41420-022-00815-x

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

Cell Death Discov. 2022 Jan 21;8(1):32. doi: 10.1038/s41420-022-00815-x.

Authors

Jianbing Hou^{1

2}, Pan Huang^{1

2}, Chao Lan^{1

2}, Shengjun Geng^{1

2}, Minghao Xu^{1

2}, Yudong Liu^{1

2}, Hongbo Chang^{1

2}, Zhongze Wang^{1

2}, Hongyu Gu^{1

2}, Yi Wang³, Guang Yang⁴, Hongjuan Cui^{5

6

7}

Affiliations

¹ State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China.
² Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing, 400716, China.
³ The Affiliated Hospital of Southwest University (The Ninth People's Hospital of Chongqing), Chongqing, China.
⁴ The Affiliated Hospital of Southwest University (The Ninth People's Hospital of Chongqing), Chongqing, China. 1640823518@qq.com.
⁵ State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, 400716, China. hongjuan.cui@gmail.com.
⁶ Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing, 400716, China. hongjuan.cui@gmail.com.
⁷ The Affiliated Hospital of Southwest University (The Ninth People's Hospital of Chongqing), Chongqing, China. hongjuan.cui@gmail.com.

Abstract

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.