1. Geniposide inhibits proliferation and induces apoptosis of diffuse large B-cell lymphoma cells by inactivating the HCP5/miR-27b-3p/MET axis
- Author
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Qiliang Lu, Yang Liu, Zhi Zeng, Lifen Zhu, Linjun Hu, Xin Liu, Qiuran Xu, Junjun Zhao, and Xiangmin Tong
- Subjects
03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,immune system diseases ,Cell Line, Tumor ,hemic and lymphatic diseases ,medicine ,Humans ,Gene silencing ,Iridoids ,HCP5 ,Gene Silencing ,miR-27b-3p ,Gene knockdown ,Geniposide ,Chemistry ,Cell growth ,apoptosis ,General Medicine ,Proto-Oncogene Proteins c-met ,medicine.disease ,Squamous carcinoma ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,cell proliferation ,Cell culture ,Apoptosis ,DLBCL ,Case-Control Studies ,Gene Knockdown Techniques ,MET ,Cancer research ,RNA, Long Noncoding ,030211 gastroenterology & hepatology ,Lymph Nodes ,Lymphoma, Large B-Cell, Diffuse ,Drug Screening Assays, Antitumor ,Diffuse large B-cell lymphoma ,Research Paper ,Signal Transduction - Abstract
Diffuse large B-cell lymphoma (DLBCL) is commonly treated with R-CHOP, but ~30 to 50% of the patients are poorly responsive to this strategy. Geniposide, an extract from the Gardenia jasminoides Ellis, plays antitumor roles in human gastric cancer, hepatocellular carcinoma, and oral squamous carcinoma. However, the effects of geniposide treatment on DLBCL cells, as well as its underlying mechanism, are still unknown. Here, we found that geniposide inhibited the proliferation of OCI-LY7 and OCI-LY3 cells in a dose-dependent manner. Furthermore, geniposide increased the percentage of apoptotic cells and upregulated the levels of cleaved PARP and cleaved caspase-3 in DLBCL cells. Interestingly, geniposide treatment significantly reduced the expression of the long noncoding RNA HLA complex P5 (lncRNA HCP5) in DLBCL cells. HCP5 expression was revealed to be upregulated in DLBCL tissues and cell lines. Moreover, HCP5 knockdown resulted in proliferation inhibition and apoptosis in OCI-LY7 and OCI-LY3 cells. miR-27b-3p was predicted as a potential target of HCP5 using the lnCAR web tool. Both HCP5 silencing and geniposide treatment increased the level of miR-27b-3p in DLBCL cells. Accordingly, a luciferase reporter assay identified miR-27b-3p as a direct target of HCP5. The expression of miR-27b-3p was upregulated and inversely correlated with the HCP5 level in DLBCL tissues. HCP5 knockdown reduced MET protein expression, which was subsequently rescued by miR-27b-3p silencing in DLBCL cells. Importantly, the restoration of MET partially reversed the geniposide-induced proliferation inhibition and apoptosis of DLBCL cells. In conclusion, geniposide inhibits the proliferation and induces the apoptosis of DLBCL cells at least partially by regulating the HCP5/miR-27b-3p/MET axis, indicating a potential strategy for DLBCL treatment.
- Published
- 2020