Journal
CANCER LETTERS
Volume 449, Issue -, Pages 226-236Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2019.02.026
Keywords
miR-1265; AMPK; Organoid; Gastric cancer
Categories
Funding
- National Natural Science Foundation of China [81572362]
- National Natural Science Foundation Project of International Cooperation (NSFC-NIH) [81361120398]
- Primary Research & Development Plan of Jiangsu Province [BE2016786]
- Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) [JX10231801]
- 333 Project of Jiangsu Province [BRA2015474]
- Jiangsu Key Medical Discipline (General Surgery) [ZDXKA2016005]
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University
Ask authors/readers for more resources
Increasing evidence indicates that microRNAs (miRNAs) play an important role in various tumors by regulating downstream target genes and diverse signaling pathways. Herein, we confirmed miR-1265 expression in gastric cancer (GC) using the Cancer Genome Atlas (TCGA) database and assessed the level of miR-1265 expression in clinical specimens and cell lines. We found that miR-1265 expression was negatively correlated with tumor size. Further functional analysis revealed that miR-1265 suppresses cellular proliferation and autophagy while inducing apoptosis in GC cells. A luciferase reporter assay was used to identify an miR-1265 targeted gene, calcium binding protein 39 (CAB39), which is an essential upstream regulator in the AMPK-mTOR signaling pathway. Upregulation or downregulation of CAB39 expression reversed the effects of miR-1265 overexpression or inhibition, respectively. Notably, the knockdown of autophagy-related gene 12 (ATG12) impaired the effects of miR-1265 inhibition or CAB39 overexpression in GC. MiR-1265 also suppressed the growth of GC cells in vivo and that of human gastric organoids. Altogether, our results show that miR-1265 suppresses GC progression and oncogenic autophagy by reducing CAB39 expression and regulating the AMPK-mTOR signaling pathway. Therefore, miR-1265 may represent a potential therapeutic target for GC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available