Rutin attenuates Sorafenib-induced Chemoresistance and Autophagy in Hepatocellular Carcinoma by regulating BANCR/miRNA-590-5P/OLR1 Axis
| Autor: | Yi Lv, Xianfeng Shen, Haoming Lan, Yanzhi Zhu, Meng Zhou, Jun Hu, Linsheng Huang, Gan Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Sorafenib
Male Carcinoma Hepatocellular Hepatocellular carcinoma Rutin Mice Nude Antineoplastic Agents Applied Microbiology and Biotechnology chemistry.chemical_compound microRNA medicine OLR1 Autophagy Animals Humans Non-coding RNA Molecular Biology Ecology Evolution Behavior and Systematics Gene knockdown Mice Inbred BALB C Chemistry Liver Neoplasms Cell Biology Hep G2 Cells Scavenger Receptors Class E Xenograft Model Antitumor Assays MicroRNAs Cell culture Drug Resistance Neoplasm Drug resistance Cancer research RNA Long Noncoding Developmental Biology medicine.drug Research Paper |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| Popis: | Rutin, the main component of Potentilla discolor Bunge, was proven to exhibit anti-tumor properties. Sorafenib (SO) is conventionally used in chemotherapy against hepatocellular carcinoma (HCC), but acquired resistance developed during long-term therapy limits its benefits. This study aimed to explore the molecular mechanism of rutin in SO-induced autophagy and chemoresistance in HCC. Sixty-eight paired HCC patients who received the same chemotherapy treatment were obtained. We also established two SO resistance cell lines and then utilized high-throughput RNA sequencing to explore their long non-coding RNA (lncRNA) expression profiles. The target microRNA (miRNA) and downstream mRNA were also explored. Our results indicated that rutin treatment attenuates autophagy and BANCR expression in SO resistance cells. Transmission electron microscopy clearly showed a significantly decreased number of autophagosomes after rutin-treated HepG2/SO and HCCLM3/SO cells. BANCR knockdown promotes the sensitivity of SO resistance cells to SO. Further study found that BANCR acts as a molecular sponge of miR-590-5P to sequester miR-590-5P away from oxidized low-density lipoprotein receptor 1 (OLR1) in HCC cells. Furthermore, in vivo study demonstrated that rutin could inhibit autophagy through the BANCR/miRNA-590-5P/OLR1 axis. Our findings suggest that rutin could regulate autophagy by regulating BANCR/miRNA-590-5P/OLR1 axis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|