期刊
AUTOPHAGY
卷 16, 期 4, 页码 659-671出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2019.1634945
关键词
Cell death; ceRNA; circRNA; HIPK3; prognosis; STK11
类别
资金
- National Institutes of Health [R01CA154365, U01CA157715, R21CA205414]
- University of Michigan's Cancer Center Support Grant [P30 CA46592]
- University of Michigan's Cancer Center Thoracic Oncology Program Research Grant
- University of Michigan Department of Surgery RAC grant
- China Scholarship Council (CSC)
The role of circular RNA in cancer is emerging. A newly reported circular RNA HIPK3 (circHIPK3) is critical in cell proliferation of various cancer types, although its role in non-small cell lung cancer (NSCLC), has yet to be elucidated. Our results provided evidence that silencing of circHIPK3 significantly impaired cell proliferation, migration, invasion and induced macroautophagy/autophagy. Mechanistically, we uncovered that autophagy was induced upon loss of circHIPK3 via the MIR124-3p-STAT3-PRKAA/AMPKa axis in STK11 mutant lung cancer cell lines (A549 and H838). STAT3 abrogation as well as transfection with a MIR124-3p mimic, recapitulated the induction of autophagy. We also demonstrated antagonistic regulation on autophagy between circHIPK3 and linear HIPK3 (linHIPK3). We therefore propose that the ratio between circHIPK3 and linHIPK3 (C:L ratio) may reflect autophagy levels in cancer cells. We observed that a high C:L ratio (>0.49) was an indicator of poor survival, especially in advanced-stage NSCLC patients. These results support that circHIPK3 is a key autophagy regulator in a subset of lung cancer and has potential clinical use as a prognostic factor. The circular RNA HIPK3 (circHIPK3) functions as an oncogene and autophagy regulator may potential use as a prognostic marker and therapeutic target in lung cancer.
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