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MiR-148a Functions as a Tumor Suppressor by Targeting CCK-BR via Inactivating STAT3 and Akt in Human Gastric Cancer.
- Source :
-
PloS one [PLoS One] 2016 Aug 12; Vol. 11 (8), pp. e0158961. Date of Electronic Publication: 2016 Aug 12 (Print Publication: 2016). - Publication Year :
- 2016
-
Abstract
- MicroRNAs (miRNAs) have been widely accepted as a class of gene expression regulators which post-translationally regulate protein expression. These small noncoding RNAs have been proved closely involved in the modulation of various pathobiological processes in cancer. In this research, we demonstrated that miR-148a expression was significantly down-regulated in gastric cancer tissues in comparison with the matched normal mucosal tissues, and its expression was statistically associated with lymph node metastasis. Ectopic expression of miR-148a inhibited tumor cell proliferation and migration in vitro, and inhibited tumor formation in vivo. Subsequently, we identified cholecystokinin B receptor (CCK-BR) as a direct target of miR-148a using western blot and luciferase activity assay. More importantly, siRNA-induced knockdown of CCK-BR elicited similar anti-oncogenic effects (decreased proliferation and migration) as those induced by enforced miR-148a expression. We also found that miR-148a-mediated anti-cancer effects are dependent on the inhibition of STAT3 and Akt activation, which subsequently regulates the pathways involved in cell proliferation and migration. Taken together, our results suggest that miR-148a serves as a tumor suppressor in human gastric carcinogenesis by targeting CCK-BR via inactivating STAT3 and Akt.
- Subjects :
- Animals
Apoptosis
Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Blotting, Western
Cell Movement
Cell Proliferation
Female
Humans
Immunoenzyme Techniques
Lymphatic Metastasis
Male
Mice
Mice, Nude
Middle Aged
Neoplasm Invasiveness
Neoplasm Staging
Prognosis
Proto-Oncogene Proteins c-akt genetics
Proto-Oncogene Proteins c-akt metabolism
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Receptor, Cholecystokinin B genetics
Reverse Transcriptase Polymerase Chain Reaction
STAT3 Transcription Factor genetics
STAT3 Transcription Factor metabolism
Stomach Neoplasms genetics
Stomach Neoplasms metabolism
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Gene Expression Regulation, Neoplastic
MicroRNAs genetics
Proto-Oncogene Proteins c-akt antagonists & inhibitors
Receptor, Cholecystokinin B metabolism
STAT3 Transcription Factor antagonists & inhibitors
Stomach Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 27518872
- Full Text :
- https://doi.org/10.1371/journal.pone.0158961