lncRNA MIR503HG inhibits cell proliferation and promotes apoptosis in TNBC cells via the miR-224-5p/HOXA9 axis.

Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer. This study investigated the molecular mechanism and influences of MIR503HG, miR-224-5p, and homeobox A9 (HOXA9) on TNBC cell growth and migration. Dual-luciferase reporter gene and RNA immunoprecipitation were performed to examine the regulation of MIR503HG, miR-224-5p, and HOXA9. Cell proliferation, apoptosis, migration, and invasion were evaluated by colony formation, flow cytometry, and Transwell assays. Finally, nude mice were employed to investigate the influence of MIR503HG on TNBC tumor growth. HOXA9 protein levels were detected by immunohistochemical staining. MIR503HG and HOXA9 expression were reduced in TNBC, while miR-224-5p was increased. Overexpression of MIR503HG or HOXA9 reduced the cell migration ability and proliferation and promoted apoptosis, and knockdown of MIR503HG or overexpression of miR-224-5p exhibited the opposite effects. Furthermore, MIR503HG promoted HOXA9 expression by inhibiting miR-224-5p. Overexpression of miR-224-5p reversed the effects of MIR503HG overexpression on TNBC cells, while overexpression of HOXA9 reversed the effect of MIR503HG knockdown. Additionally, an in vivo study proved that MIR503HG inhibited TNBC tumor growth via the miR-224-5p/HOXA9 axis. MIR503HG inhibited cell proliferation and promoted the apoptosis of TNBC cells via the miR-224-5p/HOXA9 axis, which may function as a novel target for the treatment of TNBC.

Wang SM ，Pang J ，Zhang KJ ，Zhou ZY ，Chen FY ... -  《Molecular Therapy-Oncolytics》

Knockdown of lncRNA MIR503HG suppresses proliferation and promotes apoptosis of non-small cell lung cancer cells by regulating miR-489-3p and miR-625-5p.

The long noncoding RNA (lncRNA) MIR503HG has been shown to play an important role in cancer development. The aim of the present study was to investigate the potential roles of MIR503HG in the proliferation and apoptosis of non-small cell lung cancer cell (NSCLC). We used short hairpin RNA (shRNA) against MIR503HG to knock down and vector containing full length of MIR503HG to overexpress MIR503HG in NSCLC cells. The expression of MIR503HG in NSCLC tissues and cells was detected and the effects of MIR503HG on the cell proliferation and apoptosis were determined. Results showed that the expression of MIR503HG was significantly upregulated in NSCLC tissues compared with adjacent tissues. We found that downregulation of MIR503HG could clearly suppressed cell proliferation and cell cycle progression. Moreover, MIR503HG knockdown also promoted apoptosis of NSCLC cells. As expected, overexpression of MIR503HG significantly promoted cell proliferation and inhibited cell apoptosis in NSCLC NCI-H1975 cells. We predicted and verified miR-489-3p and miR-625-5p as the direct targets of MIR503HG by bioinformatics analysis and luciferase reporter assay. Mechanically, MIR503HG negatively regulated miR-489-3p and miR-625-5p expressions in NSCLC cells. Moreover, downregulation of miR-489-3p and miR-625-5p weaken the decreased cell proliferation and increased apoptosis of A549 cells after MIR503HG knocking down. In conclusion, knockdown of MIR503HG suppressed proliferation and promoted apoptosis of NSCLC cells through regulating miR-489-3p and miR-625-5p. Our findings of this study suggested that MIR503HG could be a potential therapeutic target for NSCLC development.

Dao R ，Wudu M ，Hui L ，Jiang J ，Xu Y ，Ren H ，Qiu X ... -  《-》

Long Noncoding-RNA Component of Mitochondrial RNA Processing Endoribonuclease Promotes Carcinogenesis in Triple-Negative Breast Cancer Cells via the Competing Endogenous RNA Mechanism.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer. Increasing evidence supports that dysregulation of long noncoding RNAs (lncRNAs) plays a vital role in cancer progression. RNA component of mitochondrial RNA processing endoribonuclease (RMRP), a lncRNA, is characterized as a tumor-propeller in some cancers, but its mechanism in TNBC remains poorly understood. This study aimed to determine whether and how RMRP functions in TNBC. Cell proliferation was determined by cell counting kit-8 (CCK-8) and colony formation assays and cell apoptosis by flow cytometry analysis and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Cell migration and invasion were determined by transwell assays. RNA-binding protein immunoprecipitation (RIP), luciferase reporter, and RNA pulldown assays were implemented to assess the interaction of RMRP with other molecules in TNBC cells. RMRP expression was elevated in TNBC cells. RMRP knockdown repressed cell proliferation, migration, and invasion, but induced apoptosis in TNBC. In addition, RMRP was found to target microRNA-766-5p (miR-766-5p) in TNBC cells. Silencing miR-766-5p enhanced cell viability and decreased apoptosis, whereas miR-766-5p overexpression had opposite effects. Furthermore, miR-766-5p was found to bind to yes-associated protein 1 (YAP1). Moreover, miR-766-5p inhibition reversed the repressive effect of RMRP knockdown on the malignant progression of TNBC. The present study manifested that RMRP promotes the growth, migration, and invasion of TNBC cells via the miR-766-5p/YAP1 axis. These findings provide novel perspectives for TNBC treatment.

Qi L ，Sun B ，Yang B ，Lu S ... -  《-》

LncRNA SNHG6/miR-125b-5p/BMPR1B Axis: A New Therapeutic Target for Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a significant cause of patient morbidity. The exactly pathobiological features of this condition has yet to be completely elucidated. Breast cancer data obtained from The Cancer Genome Atlas (TCGA) database were evaluated for lncRNA SNHG6 expression. Normal human breast epithelial cell line (MCF-10A) and other breast cancer cell lines (BT-549, MDA-MB-231, Hs 578t, ZR-75-30, SK-BR-3, MCF-7) were also assessed for lncRNA SNHG6 expressions. Cellular proliferative ability was evaluated with colony formation and CCK-8 assays. The ability of cells to migrate was scrutinized with the wound healing and Boyden chamber cell migration assays. qRT-PCR enabled for detection of lncRNA SNHG6, miR-125b-5p and BMPR1B mRNA expressions. Protein BMPR1B expressions were further assessed using Western Blotting. Direct binding sites between transcripts were determined using dual-luciferase reporter assays. We also constructed a xenograft mouse model to further dissect the vivo implications of lncRNA SNHG6. Ki-67 and c-Caspase-3 expressions were detected using immunohistochemistry staining. Breast cancer cell lines demonstrated higher lncRNA SNHG6 expressions, particularly TNBC cell lines, in contrast to normal breast epithelial cell lines. This finding coincided with those noted on analysis of TCGA breast cancer data. lncRNA SNHG6 knockdown inhibited TNBC cell proliferation, migration, while promoted cell apoptosis. Furthermore, suppressed lncRNA SNHG6 expressions resulted in lower tumor weights and volumes in a xenograft mouse model, as evidenced by Ki-67 and c-Caspase-3 expression profiles in tumor tissues. miR-125b-5p and lncRNA SNHG6/BMPR1B both possessed direct binding sites for each other which was validated utilizing a dual-luciferase reporter assay. Decreasing lncRNA SNHG6 expression in TNBC cells upregulated miR-125b-5p expression. Another side, inhibiting miR-125b-5p upregulated BMPR1B expression in these cells. Moreover, knocking down lncRNA SNHG6 downregulated BMPR1B expression in TNBC cells, and the finding was rescued in cells which were exposed to miR-125b-5p inhibitor. Downregulating miR-125b-5p mitigated the effect of suppressing lncRNA SNHG6 on TNBC cell proliferation, migration, and apoptosis. Downregulation of lncRNA SNHG6 could inhibit TNBC cell proliferative, migratory capabilities and promote apoptosis capability, likely through modulation of the miR-125b-5p/BMPR1B axis. This axis may be targeted in formulating new therapies for TNBC.

Lv Y ，Lv X ，Yang H ，Qi X ，Wang X ，Li C ，Shang X ，Guo H ，Zhang J ，Zhang Y ... -  《Frontiers in Oncology》

Long non-coding RNA MIR503HG inhibits the proliferation, migration and invasion of colon cancer cells via miR-107/Par4 axis.

Colon cancer is a common caner with high death rate in the world. The study aimed to detect the effect and mechanism of long non-coding RNA (LncRNA) MIR503HG on colon cancer. The MIR503HG expression was measured in colon cancer tissues and cell lines by qRT-PCR. The proliferation, apoptosis, migration and invasion of colon cancer cells were measured by MTT, flow-cytometry, wound healing and transwell assay. The protein expression of E-cadherin, N-cadherin, and Vimentin was detected by Western blot. The target relationships among MIR503HG, miR-107 and Par4 were predicted by StarBase and TargetScan, and verified by luciferase reporter and RNA pull-down assay. The xenograft tumor model was constructed in mice to verify the inhibitory effect of MIR503HG in vivo. The expression of MIR503HG was decreased in colon cancer tissues and cell lines. MIR503HG overexpression inhibited cell proliferation, migration and invasion, promoted cell apoptosis, down-regulated N-cadherin and Vimentin, and up-regulated E-cadherin in colon cancer. MIR503HG negatively regulated its target miR-107. MiR-107 overexpression reversed the anti-tumor effects of MIR503HG overexpression on colon cancer cells. Par4 was a target of miR-107, which was positively regulated by MIR503HG. The promoting effects of MIR503HG silencing on colon cancer cells were eliminated by Par4 overexpression. MIR503HG regulated Par4 via sponging miR-107 in colon cancer, which promoting a new idea for the treatment of colon cancer.

Han H ，Li H ，Zhou J 《-》