MicroRNA-145 exerts tumor-suppressive and chemo-resistance lowering effects by targeting CD44 in gastric cancer

• Published in: World journal of gastroenterology : WJG 2017-04, Vol.23 (13), p.2337-2345
• Main Authors: Zeng, Jian-Feng, Ma, Xiao-Qiu, Wang, Lin-Pei, Wang, Wei
• Format: Article
• Language: English
• Subjects: Basic Study; Cell Line, Tumor; Cell Self Renewal; Drug Resistance, Neoplasm; Humans; Hyaluronan Receptors - metabolism; MicroRNAs - metabolism; Stomach Neoplasms - metabolism
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v23.i13.2337

To determine the potential roles of CD4 and microRNA (miR)-145 in gastric cancer. The levels of CD44 and miR-145 were determined in gastric cancer cells. Quantitative real-time polymerase chain reaction was used to measure to the level of CD44 mRNA. A luciferase reporter assay and western blotting were performed to examine the effect of miR-145 on CD44 expression. Tumor sphere and MTT assays were carried out to evaluate the self-renewal and chemo-resistance properties of gastric cancer cells. The expression of CD44 was greatly increased and miR-145 was decreased in gastric cancer cells that were highly enriched in cancer stem cells (CSCs). The results demonstrated that miR-145 regulated CD44 by targeting directly the CD44 3'-untranslated region (3'-UTR). In gastric cancer cells, overexpression of miR-145 repressed the activity of the CD44 3'-UTR, and disruption of miR-145/CD44 3'-UTR interactions abrogated the silencing effects. In addition, miR-145 inhibition stimulated CD44 3'-UTR activity and disruption of miR-145/CD44 3'-UTR interactions abrogated this stimulatory effect. Enforced CD44 expression greatly increased tumor sphere formation and chemo-resistance in gastric cancer cells. Furthermore, the inhibition of CSCs and the chemo-sensitivity of gastric cancer cells treated with miR-145 were significantly abrogated by overexpression of CD44. miR-145 targeting of CD44 plays critical roles in the regulation of tumor growth and chemo-resistance in gastric cancer.