[Long intergenic non-coding RNA 01121 promotes metastasis of prostate cancer cells by activating the EMT process].

OBJECTIVE: To investigate the expression, biological function and potential mechanism of long intergenic non-coding RNA 01121 (LINC01121) in PCa. METHODS: Using real-time quantitative polymerase chain reaction (qRT-PCR), we detected the expression of LINC01121 in PCa cell lines and the efficiency of small interfering RNA (siRNA) in knocking down LINC01121. We examined the biological function of LIC01121 in the PCa cells by CCK8, cell cloning, and Transwell migration and invasion assays, and determined the expressions of epithelial-mesenchymal transition (EMT)-related proteins in the PCa cells by Western blot. RESULTS: The relative expression of LINC01121 was significantly higher in the PCa than in the WPMY1 human normal prostate matrix immortalized cells (P < 0.05). Knocking down the expression of LINC01121 significantly reduced the proliferation, cloning, migration and invasiveness of the PCa cells (P < 0.05), down-regulated the expressions of the N-cadherin and vimentin proteins and up-regulated that of E-cadherin in the PCa cells (P < 0.05). CONCLUSION: LINC01121 is overexpressed in PCa cell lines, which may promote the proliferation, migration and invasiveness of the cells by activating the EMT process.

LINC01121 induced intervertebral disc degeneration via modulating miR-150-5p/MMP16 axis.

BACKGROUND: Growing evidence indicates that Long noncoding RNAs contribute to cell differentiation, invasion, metabolism, proliferation and metastasis. However, the potential role of LINC01121 in progression of intervertebral disc degeneration (IDD) remains unclear. METHODS: LINC01121, matrix metalloprotease (MMP)-16 and miR-150-5p expression was determined by a quantitative-reverse transcriptase-polymerase chain reaction assay. Inflammatory cytokines level was measured by an enzyme-linked immunosorbent assay and cell counting kit-8 analysis was used to assess cell proliferation. MMP-16-specific binding with miR-150-5p was verified with a luciferase reporter assay. RESULTS: We noted that interleukin (IL)-1ß and tumor necrosis factor (TNF)-α treatment enhanced LINC01121 and MMP-16 expression in nucleus pulposus (NP) cells. LINC01121 was higher in IDD specimens compared to that in control specimens. Higher expression of LINC01121 was correlated with disc degeneration degree. Ectopic expression of LINC01121 enhanced cell proliferation and promoted ki-67, MMP-3 and ADAMTS5 expression and also suppressed collagen II expression in NP cells. We observed that overexpression of LINC01121 increased the secretion of three inflammatory cytokines, including IL-6, TNF-α and IL-1ß. We found that ectopic expression of LINC01121 decreased the miR-150-5p level in NP cells. Luciferase reporter data confirmed that MMP-16 was one direct target of miR-150-5p. Overexpression of miR-150-5p inhibited MMP-16 level and elevated the expression of LINC01121 enhanced MMP-16 level. We also found that MMP-16 was up-regulated in IDD specimens compared to that in control specimens. Higher expression of MMP-16 was correlated with disc degeneration degree. Interestingly, MMP-16 expression was positively related to LINC01121 in IDD specimens. Finally, overexpression of LINC01121 regulated cell growth, extracellular matrix degradation and inflammatory cytokine secretion via modulating MMP-16. CONCLUSIONS: our data suggested LINC01121 may be a new therapeutic target for IDD.

LINC01121 Inhibits Cell Apoptosis While Facilitating Proliferation, Migration, and Invasion Though Negative Regulation of the Camp/PKA Signaling Pathway via GLP1R.

BACKGROUND/AIMS: Pancreatic cancer is an aggressive malignancy as a result of highly metastatic potential. The current study was carried out to alter the expression of LINC01121 in pancreatic cancer, with the aim of elucidating its effects on the biological processes of cell proliferation, migration, invasion, and apoptosis. We hypothesized that both the GLP1R gene and cAMP/PKA signaling pathway participate in the aforementioned process. METHODS: Microarray data (GSE14245, GSE27890 and GSE16515) and annotating probe files linked to pancreatic cancer were downloaded through the GEO database. The Multi Experiment Matrix (MEM) site was used to predict the target gene of lncRNA. Both pancreatic cancer tissues (n = 56) and paracancerous tissues (n = 45) were collected from patients diagnosed with pancreatic cancer. Immunohistochemistry was applied to identify the positive expression rate of GLP1R protein. Isolated pancreatic cancer cells and PANC-1 cells were independently classified into the blank, negative control (NC), LINC01121 vector, siRNA-LINC01121, siRNA-GLP1R and siRNA-LINC01121 + siRNA-GLP1R groups. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were applied to detect the expressions of LINC01121, GLP1R, cAMP, PKA, CREB, Bcl-2, Bad and PCNA. Cell proliferation, migration, invasion, cycle progression, and apoptosis were examined by MTT assay, scratch test, Transwell assay and flow cytometry analyses of Annexin V-FITC/PI staining. RESULTS: Observations were made indicating that LINC01121 was highly expressed, while low expressions of GLP1R in pancreatic cancer were detected based on microarray data, which was largely in consistent with the data collected of LINC01121 and GLP1R within the tissues. The target prediction program and luciferase activity analysis was testament to the notion suggesting that GLP1R was indeed a target of LINC01121. In contrast to the blank and NC groups, the LINC01121 vector group exhibited increased expressions of LINC01121; decreased mRNA and protein levels of GLP1R, Bad, cAMP, and PKA; increased protein levels of CREB, Bcl-2, PCNA, p-PKA and p-CREB; increased cell proliferation, migration and invasion; and decreased cell apoptosis. There was no significant difference detected among the blank, NC, and siRNA-LINC01121 + siRNA-GLP1R groups, except that decreased LINC01121 expression was determined in the siRNA-LINC01121 + siRNA-GLP1R group. Parallel data were observed in the pancreatic cancer cells and PANC-1 cells. CONCLUSION: The current study presents evidence indicating that LINC01121 might inhibit apoptosis while acting to promote proliferation, migration, and invasion of pancreatic cancer cells, supplementing the stance held that LINC01121 functions as a tumor promoter by means of its involvement in the process of translational repression of the GLP1R and inhibition of the cAMP/PKA signaling pathway.

Long Intergenic Non-Coding RNA 01121 Promotes Breast Cancer Cell Proliferation, Migration, and Invasion via the miR-150-5p/HMGA2 Axis.

PURPOSE: Long intergenic noncoding RNA 01121 (LINC01121) has been reported to be aberrantly expressed and acts as an oncogene in pancreatic cancer. However, the detailed molecular mechanism of LINC01121 in breast cancer remains largely unclear. In this study, we aimed to investigate the expression and biological function of LINC01121 in breast cancer. METHODS: LINC01121 and miR-150-5p expression were measured in breast cancer cell lines using quantitative reverse transcription PCR. MTS and flow cytometry assays were performed to determine cell proliferation, the cell cycle, and apoptosis. Cell migration and invasion were assessed by transwell assay. The protein expression of HMGA2 in breast cancer cell lines was measured by Western blotting. A luciferase reporter assay was used to assess the binding of LINC01121 and miR-150-5p. RESULTS: We found that LINC01121 was markedly up-regulated in breast cancer cell lines compared with normal breast epithelial cells. LINC01121 down-regulation markedly suppressed cell proliferation, cell cycle progression, migration, and invasion and promoted apoptosis in breast cancer cells. Further investigation showed that LINC01121 could serve as a molecular sponge for miR-150-5p and indirectly modulate the expression of its target, HMGA2. Moreover, miR-150-5p knockdown rescued the effects of LINC01121 down-regulation on HMGA2 protein expression, cell proliferation, cell cycle progression, apoptosis, migration, and invasion in breast cancer cells. CONCLUSION: Knockdown LINC01121 inhibited breast cancer cell proliferation, migration, and invasion via the miR-150-5p/HMGA2 axis.