Geniposide inhibits proliferation and induces apoptosis of diffuse large B-cell lymphoma cells by inactivating the HCP5/miR-27b-3p/MET axis.

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.

Hu L ，Zhao J ，Liu Y ，Liu X ，Lu Q ，Zeng Z ，Zhu L ，Tong X ，Xu Q ... -  《International Journal of Medical Sciences》

LncRNA CHROMR/miR-27b-3p/MET axis promotes the proliferation, invasion, and contributes to rituximab resistance in diffuse large B-cell lymphoma.

Liu C ，Zhao X ，Wang Z ，Zhang C ，Zheng W ，Zhu X ，Zhang D ，Gong T ，Zhao H ，Li F ，Guan T ，Guo X ，Zhang H ，Yu B ... -  《-》

Long non-coding RNA SNHG16 promotes proliferation and inhibits apoptosis of diffuse large B-cell lymphoma cells by targeting miR-497-5p/PIM1 axis.

The aberrant expression and dysfunction of long non-coding RNAs (lncRNAs) have been identified as critical factors governing the initiation and progression of different human cancers, including diffuse large B-cell lymphoma (DLBCL). LncRNA small nucleolar RNA host gene 16 (SNHG16) has been recognized as a tumour-promoting factor in various types of cancer. However, the biological role of SNHG16 and its underlying mechanism are still unknown in DLBCL. Here we disclosed that SNHG16 was overexpressed in DLBCL tissues and the derived cell lines. SNHG16 knockdown significantly suppressed cell proliferation and cell cycle progression, and it induced apoptosis of DLBCL cells in vitro. Furthermore, silencing of SNHG16 markedly repressed in vivo growth of OCI-LY7 cells. Mechanistically, SNHG16 directly interacted with miR-497-5p by acting as a competing endogenous RNA (ceRNA) and inversely regulated the abundance of miR-497-5p in DLBCL cells. Moreover, the proto-oncogene proviral integration site for Moloney murine leukaemia virus 1 (PIM1) was identified as a novel direct target of miR-497-5p. SNHG16 overexpression rescued miR-497-5p-induced down-regulation of PIM1 in DLBCL cells. Importantly, restoration of PIM1 expression reversed SNHG16 knockdown-induced inhibition of proliferation, G0/G1 phase arrest and apoptosis of OCI-LY7 cells. Our study suggests that the SNHG16/miR-497-5p/PIM1 axis may provide promising therapeutic targets for DLBCL progression.

Zhu Q ，Li Y ，Guo Y ，Hu L ，Xiao Z ，Liu X ，Wang J ，Xu Q ，Tong X ... -  《-》

Silencing of long non-coding RNA HCP5 inhibits proliferation, invasion, migration, and promotes apoptosis via regulation of miR-299-3p/SMAD5 axis in gastric cancer cells.

Yin D ，Lu X 《-》

The Effect of Long Non-Coding RNA (lncRNA) HCP5 on Regulating Epithelial-Mesenchymal Transition (EMT)-Related Markers in Gastric Carcinoma Is Partially Reversed by miR-27b-3p.

Chen S ，Ren C ，Zheng H ，Sun X ，Dai J ... -  《MEDICAL SCIENCE MONITOR》