| First Author | Shao L | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 1 | Pages | 264-274 |
| PubMed ID | 29985646 | Mgi Jnum | J:283785 |
| Mgi Id | MGI:6388111 | Doi | 10.1096/fj.201701456RR |
| Citation | Shao L, et al. (2019) Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer. FASEB J 33(1):264-274 |
| abstractText | Helicobacter pylori infection is a major risk factor for the development of gastric cancer. Aberrant expression of microRNAs is strongly implicated in gastric tumorigenesis; however, their contribution in response to H. pylori infection has not been fully elucidated. In this study, we evaluated the expression of miR-135b-5p and its role in gastric cancer. We describe the overexpression of miR-135b-5p in human gastric cancer tissue samples compared with normal tissue samples. Furthermore, we found that miR-135b-5p is also up-regulated in gastric tumors from the trefoil factor 1-knockout mouse model. Infection with H. pylori induced the expression of miR-135b-5p in the in vitro and in vivo models. miR-135b-5p induction was mediated by NF-kappaB. Treatment of gastric cancer cells with TNF-alpha induced miR-135b-5p in a NF-kappaB-dependent manner. Mechanistically, we found that miR-135b-5p targets Kruppel-like factor 4 (KLF4) and binds to its 3' UTR, leading to reduced KLF4 expression. Functionally, high levels of miR-135b-5p suppress apoptosis and induce cisplatin resistance. Our results uncovered a mechanistic link between H. pylori infection and miR-135b-5p-KLF4, suggesting that targeting miR-135b-5p could be a potential therapeutic approach to circumvent resistance to cisplatin.-Shao, L., Chen, Z., Soutto, M., Zhu, S., Lu, H., Romero-Gallo, J., Peek, R., Zhang, S., El-Rifai, W. Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer. |
