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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Yang, Suzhen Zhang, Jing Chen, Di Cao, Jiayi Zheng, Ying Han, Yuying Jin, Yirong Wang, Shuhui Wang, Ting Ma, Lin Luo, Tingting Wang, Yan Qin, Wen Dong, Lei |
| Abstract | Background The role of CARM1 in tumors is inconsistent. It acts as an oncogene in most cancers but it inhibits the progression of liver and pancreatic cancers. CARM1 has recently been reported to regulate autophagy, but this function is also context-dependent. However, the effect of CARM1 on gastric cancer (GC) has not been studied. We aimed to explore whether CARM1 was involved in the progression of GC by regulating autophagy. Methods The clinical values of CARM1 and autophagy in GC were evaluated by immunohistochemistry and qRT–PCR. Transmission electron microscopy, immunofluorescence and western blotting were employed to identify autophagy. The role of CARM1 in GC was investigated by CCK-8, colony formation and flow cytometry assays in vitro and a xenograft model in vivo. Immunoprecipitation assays were performed to determine the interaction of CARM1 and TFE3. Results CARM1 was upregulated in clinical GC tissues and cell lines, and higher CARM1 expression predicted worse prognosis. CARM1 enhanced GC cell proliferation, facilitated G1-S transition and inhibited ER stress-induced apoptosis by regulating autophagy. Importantly, treatment with a CARM1 inhibitor rescued the tumor-promoting effects of CARM1 both in vitro and in vivo. Furthermore, we demonstrated that CARM1 promoted TFE3 nuclear translocation to induce autophagy through the cytoplasmic AMPK-mTOR and nuclear AMPK-CARM1-TFE3 signaling pathways. Conclusion CARM1 promoted GC cell proliferation, accelerated G1-S transition and reduced ER stress-induced apoptosis by regulating autophagy. Mechanistically, CARM1 triggered autophagy by facilitating TFE3 nuclear translocation through the AMPK-mTOR and AMPK-CARM1-TFE3 signaling pathways. |
| Related Links | https://cancerci.biomedcentral.com/counter/pdf/10.1186/s12935-022-02522-0.pdf |
| Ending Page | 22 |
| Page Count | 22 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14752867 |
| DOI | 10.1186/s12935-022-02522-0 |
| Journal | Cancer Cell International |
| Issue Number | 1 |
| Volume Number | 22 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2022-03-04 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Cell Biology Autophagy CARM1 TFE3 AMPK Gastric cancer |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Genetics Oncology |
| Journal Impact Factor | 5.3/2023 |
| 5-Year Journal Impact Factor | 5/2023 |
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