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 ... -  《-》

Long non-coding RNA LINC01003 suppresses the development of multiple myeloma by targeting miR-33a-5p/PIM1 axis.

Numerous long non-coding RNAs (lncRNAs) are reported to affect the progression of multiple myeloma (MM). This study is aimed to explore the role and downstream mechanism of lncRNA LINC01003 in MM. Xenograft tumor assay was used to assess the function of LINC01003 in MM in vivo. The mRNA expression levels of LINC01003, miR-33a-5p, and PIM1 were determined by quantitative real-time polymerase chain reaction. Cell viability was examined by MTT assay. Relative protein levels of apoptosis-related factors (Bcl-2 and Bax) and proviral integration site of the Moloney leukemia virus kinase 1 (PIM1) were detected via western blot. Adhesion-related proteins were measured by Enzyme-linked immunosorbent assay was used to determine the levels of adhesion-related proteins. Besides, the target relation among LINC01003, miR-33a-5p and PIM1 was tested via dual-luciferase reporter assay. Low expression of LINC01003 was observed in MM cell lines and peripheral blood samples of MM patients. Both LINC01003 up-regulation and miR-33a-5p down-regulation repressed cell viability and adhesion, and promoted apoptosis of MM cells. Moreover, LINC01003 suppressed the growth of xenograft tumor in mice. We then identified miR-33a-5p as a downstream target of LINC01003, and confirmed that PIM1 was a direct target gene of miR-33a-5p. Both high expression of miR-33a-5p and low expression of PIM1 reversed the suppressive effects of LINC01003 overexpression on cell adhesion and viability, and the promoting effect on apoptosis in MM cells. LINC01003 functioned as a sponge of miR-33a-5p to inhibit the development MM by regulating PIM1 expression.

Wu L ，Xia L ，Chen X ，Ruan M ，Li L ，Xia R ... -  《-》

LncRNA SNHG16 promotes proliferation, migration and invasion of osteosarcoma cells by targeting miR-1301/BCL9 axis.

Long non-coding RNAs (lncRNAs) play a key role in regulating tumor growth and metastasis of osteosarcoma (OS). Recent studies have reported that lncRNA small nucleolar RNA host gene 16 (SNHG16) is highly expressed in OS tissues and contributes to the proliferation, migration and invasion of OS cells. However, the molecular mechanism involved in the oncogenic role of SNHG16 in OS remains poorly known. In the current study, we confirmed that SNHG16 expression was markedly up-regulated in OS tissues compared to paracancerous tissues. The elevated level of SNHG16 closely associated with advanced tumor stages, larger tumor size and more distance metastasis. Furthermore, OS patients with high SNHG16 level had a significant poorer overall survival compared to patients with low SNHG16 level. Knockdown of SNHG16 suppressed the proliferation, migration and invasion of U2OS and MG63 cells. Mechanistically, SNHG16 acted as a competing endogenous RNA (ceRNA) by directly interacting with miR-1301 and inversely regulated its abundance in OS cells. Notably, suppression of miR-1301 rescued SNHG16 knockdown attenuated OS cell proliferation, migration and invasion. SNHG16 knockdown reduced the expression of BCL9 protein in OS cells. Accordingly, BCL9 restoration facilitated the proliferation, migration and invasion of OS cells with SNHG16 knockdown. Collectively, these results suggest that SNHG16 is a potential prognostic biomarker for OS patients. SNHG16 promotes BCL9 expression by sponging miR-1301 to facilitate the proliferation, migration and invasion of OS cells.

Wang X ，Hu K ，Chao Y ，Wang L ... -  《-》

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》

Lnc SMAD5-AS1 as ceRNA inhibit proliferation of diffuse large B cell lymphoma via Wnt/β-catenin pathway by sponging miR-135b-5p to elevate expression of APC.

Zhao CC ，Jiao Y ，Zhang YY ，Ning J ，Zhang YR ，Xu J ，Wei W ，Kang-Sheng G ... -  《Cell Death & Disease》