Journal
ONCOLOGY LETTERS
Volume 16, Issue 2, Pages 2319-2325Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2018.8924
Keywords
microRNA-23a/27a/24-2 cluster; gastric cancer; suppressor of cytokine-induced signaling 6
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Funding
- Yen Tjing Ling Medical Foundation [CI-100-16, CI-103-14]
- Center of Excellence for Cancer Research at Taipei Veterans General Hospital [DOH101-TD-C-111-007, DOH102-TD-C-111-007, MOHW103-TD-B-111-02]
- Ministry of Education
- Aim for the Top University Plan [101AC-T406, 103AC-T607, 104AC-T506]
- Ministry of Science and Technology, Taiwan [MOST105-2319-B-010-001]
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Previous studies have indicated that certain microRNAs (miRNAs/miRs) function as either tumor suppressors or oncogenes in human cancer. The present study identified the miR-23a/27a/24-2 cluster, containing miR-23, miR-27a and miR-24, as an oncogene in gastric cancer. The expression of the miR-23a/27a/24-2 cluster was upregulated in clinical gastric cancer tissues. Transfection with inhibitors of miR-23a, miR-27a, or miR-24, either independently or together, repressed in vitro colony formation and in vivo tumor formation. The miR23a/27a/24-2 cluster inhibitors repressed the growth of gastric cancer cells in a synergistic manner. In addition, treatment with lower doses of the miRNA inhibitor mixture induced the formation of apoptotic bodies. According to computational predictions using TargetScan, suppressor of cytokine-induced signaling 6 (SOCS6) was identified as one of the downstream target genes of the miR-23a/27a/24-2 cluster. The expression of SOCS6 was significantly lower in tumor tissues than in matched normal tissues (P<0.01) and was associated with poor survival (P<0.00001). Taken together, these results strongly suggested that the miR-23a/27a/24-2 cluster may mediate the progression of gastric cancer through the suppression of SOCS6 expression. The present study also provides a novel molecular target for the development of an anti-gastric cancer agent.
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