LINC00958 facilitates cervical cancer cell proliferation and metastasis by sponging miR-625-5p to upregulate LRRC8E expression

Accepted as a malignant tumor worldwide, cervical cancer (CC) has attracted much attention for its high incidence and mortality rates. Previous studies have elucidated the critical regulatory function that long noncoding RNAs (lncRNAs) exert on the tumorigenesis and progression of diverse tumors. Although multiple investigations have depicted that LINC00958 has a great impact on the complex biological process of many cancers, knowledge concerning the regulatory role of LINC00958 in CC remains limited and needs to be further explored. In our study, LINC00958 expression was evidently overexpressed in CC tissues and cells. Besides this, LINC00958 negatively regulated miR-625-5p expression and was verified to bind with miR-625-5p in CC. Subsequently, it was testified by a series of experiments that LINC00958 promotes CC cell proliferation and metastasis by sponging miR-625-5p. Furthermore, the leucine-rich repeat containing the eight family member E (LRRC8E) could bind with miR-625-5p, and its expression was negatively modulated by miR-625-5p, whereas positively regulated by LINC00958 in CC. Final rescue assays verified the effects of LINC0095/LRRC8E interaction and miR-625-5p/LRRC8E interaction on CC cell proliferation and metastasis. Collectively, LINC00958 facilitates CC cell proliferation and metastasis via the miR-625-5p/LRRC8E axis.     

Downregulation of EIF5A2 by miR-221-3p inhibits cell proliferation,promotes cell cycle arrest and apoptosis in medulloblastoma cells

Recently, miR-221-3p expression has been reported to be down-regulated in medulloblastoma (MB), but its functional effects remains unclear. In this study, quantitative real-time PCR (qRT-PCR) revealed significantly decreased miR-221-3p in MB cell lines. Transfection of miR-221-3p mimics reduced, or inhibitor increased cell proliferation in MB cells using MTT assay. Flow cytometry analysis indicated miR-221-3p overexpression promoted, while knockdown alleviated G0/G1 arrest and apoptosis. Luciferase reporter assay confirmed miR-221-3p directly targets the EIF5A2 gene. Moreover, restoration of EIF5A2 in the miR-221-3p-overexpressing DAOY cells significantly alleviated the suppressive effects of miR-221-3p on cell proliferation, cell cycle and apoptosis. Furthermore, miR-221-3p overexpression decreased CDK4, Cyclin D1 and Bcl-2 and increased Bad expression, which was reversed by EIF5A2 overexpression. These results uncovered the tumor suppressive role of miR-221-3p in MB cell proliferation at least in part via targeting EIF5A2, suggesting that miR-221-3p might be a potential candidate target for diagnosis and therapeutics of MB.     

LINC01116 promotes proliferation and migration of endometrial stromal cells by targeting FOXP1 via sponging miR-9-5p in endometriosis

Endometriosis is a common multi-factorial gynaecological disease. Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in the pathogenesis of endometriosis. In the present study, the expression profiles of lncRNAs in 6 pairs of endometriosis ectopic endometrium (ecEM) and eutopic endometrium (euEM) tissues were analysed by RNA sequencing. From the profiles, LINC01116 was found to be up-regulated in ecEM tissues compared to euEM tissues and was verified by quantitative real-time PCR (qRT-PCR). Then, functional experiments demonstrated that LINC01116 promoted the proliferation and migration of ectopic primary endometrial stromal cells (ESCs), while miR-9-5p exerted the opposite effects. Dual-luciferase reporter assays verified that LINC01116 directly sponged miR-9-5p and relieved the suppression of its target, Forkhead box protein P1 (FOXP1). Rescue experiments further demonstrated that LINC01116 could promote proliferation and migration of ESCs by targeting FOXP1 via sponging miR-9-5p. Overall, our study illuminates that LINC01116 promotes the progression of endometriosis through the miR-9-5p/FOXP1 axis. This finding provides a novel therapeutic target for patients with endometriosis.     

Long noncoding RNA LINC00968 promotes endothelial cell proliferation and migration via regulating miR-9-3p expression

Long noncoding RNAs (lncRNAs) have been showed to play a crucial role in pathogenesis and development of cardiovascular diseases. Our study aimed to study the expression and functional role of lncRNA LINC00968 in the development of coronary artery disease (CAD). We showed that the LINC00968 expression level was upregulated in the CAD tissues compared with normal arterial tissues. In addition, we showed that the expression level of LINC00968 was upregulated by oxidized low-density lipoprotein (oxLDL) treatment in endothelial cell. Ectopic expression of LINC00968 regulated the proliferation and migration of endothelial cell. Moreover, we showed that overexpression of LINC00968 inhibited miR-9-3p expression in an endothelial cell. Furthermore, we demonstrated that the miR-9-3p expression was downregulated in the CAD samples compared with normal arterial tissues and the expression level of miR-9-3p was downregulated by oxLDL treatment in endothelial cell. Finally, we showed that ectopic expression of LINC00968 promoted endothelial cell proliferation and migration partly through regulating miR-9-3p expression. These results suggested that LINC00968 plays a crucial role in the progression of the CAD.     

LINC00184 plays an oncogenic role in non-small cell lung cancer via regulation of the miR-524-5p/HMGB2 axis

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. We aimed to investigate the role of LINC00184 in NSCLC. Migration, proliferation and invasion of NSCLC cells were analysed using the wound healing assay, cell counting kit-8 assay and transwell assay, respectively. Apoptosis and cell cycle were assessed using flow cytometry. Online bioinformatics tools were utilized to predict downstream microRNAs (miRNA) or genes related to LINC00184 expression. The RNA pull-down experiment and luciferase reporter assay were performed to verify the predictions thereof. LINC00184, miR-524-5p, and high mobility group 2 protein (HMGB2) expression levels in NSCLC tissues and cell lines were detected using quantitative real-time polymerase chain reaction. An NSCLC mouse model was constructed for in vivo experiments. LINC00184 overexpression was observed in NSCLC tissues and cell lines and was found to be correlated with poor prognosis. LINC00184 knockdown inhibited cell proliferation, migration and invasion, induced cell cycle arrest and accelerated apoptosis in NSCLC cell lines. LINC00184 suppressed tumour growth and proliferation in NSCLC mouse models and directly targeted the miR-524-5p/HMGB2 axis. Moreover, the expression levels of LINC00184 and HMGB2 were negatively correlated with miR-524-5p expression, whereas LINC00184 expression was positively correlated with HMGB2 expression. LINC00184 affected the cell cycle, proliferation, apoptosis, migration and invasion in NSCLC via regulation of the miR-524-5p/HMGB2 axis.     

Silencing LINC00504 inhibits cell proliferation,invasion as well as migration and promotes cell apoptosis in lung cancer cells via upregulating miR-876-3p

LINC00504 acts as an oncogene and associates with unfavorable prognosis in patients with lung cancer. Silencing LINC00504 may be a promising strategy for treatment of lung cancer and its effects were firstly investigated in lung cancer cells this study. The gene expression level of miR-876-3p as well as LINC00504 were measured via PCR assay. The cell proliferation was investigated through Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Flow cytometry was applied for detection of cell apoptosis. Wound healing and transwell assay were performed for measurement of cell migration and invasion respectively. The apoptosis related protein expressions were measured by western blot. Luciferase report assay was conducted for verification the target gene. LINC00504 was higher expressed in five types of lung cancer cells studied herein when compared with the control normal cells. LINC00504 knockdown exerted inhibitory effects on cell apoptosis, cell migration as well as cell invasion and promoted cell apoptosis. All the effects mentioned above were counteracted by miR-876-3p inhibitor. Silencing LINC00504 possessed anti-proliferation, repression of cell invasion as well as migration and pro-apoptosis effects via targeting up-regulation of miR-876-3p in lung cancer cells, proving the new therapeutic targets and highlighting the potential application in future diagnosis and treatment in lung cancer.     

CircDUS2L (circ_0039908) promotes lung adenocarcinoma progression by upregulating PGAM1 by acting as a miR-590-5p molecular sponge

Lung adenocarcinoma (LUAD) is usually found at the metastatic stage. Circular RNA dihydrouridine synthase 2-like (DUS2L) (circDUS2L) has been discovered to be upregulated in LUAD. Nevertheless, the function of circDUS2L in LUAD has not been verified. Levels of circDUS2L, microRNA-590-5p (miR-590-5p), and phosphoglycerate mutase 1 (PGAM1) mRNA were analyzed using quantitative real-time polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, metastasis, and invasion were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), colony formation, 5-ethynyl-2′-deoxyuridine (Edu), flow cytometry, and transwell assays. Protein levels were detected by western blotting. Cell glycolysis was analyzed by measuring cell glucose consumption, lactate production, and extracellular acidification rate (ECAR). The regulatory mechanism of circDUS2L in LUAD cells was analyzed by bioinformatics analysis, dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. Xenograft assay was conducted to confirm the function of circDUS2L in vivo. CircDUS2L was highly expressed in LUAD tissues and cells. CircDUS2L silencing constrained xenograft tumor growth in vivo. CircDUS2L knockdown induced apoptosis, repressed viability, colony formation, proliferation, metastasis, invasion, and glycolysis of LUAD cells in vitro by releasing miR-590-5p via functioning as a miR-590-5p sponge. MiR-590-5p was lowly expressed in LUAD tissues and cells, and miR-590-5p mimic curbed malignant behaviors and glycolysis of LUAD cells by targeting PGAM1. PGAM1 was overexpressed in LUAD tissues and cells, and circDUS2L sponged miR-590-5p to regulate PGAM1 expression. CircDUS2L elevated PGAM1 expression through functioning as a miR-590-5p sponge, thus driving malignant behaviors and glycolysis of LUAD cells.     

LINC00339 promotes gastric cancer progression by elevating DCP1A expression via inhibiting miR-377-3p

Up to date, the mechanism of gastric cancer (GC) development is poorly understood. This study was to demonstrate the effects of LINC00339 on GC progression. Here, we found that LINC00339 was overexpressed expressed in GC tissues and predicted poor outcome. By CCK8, colony formation and Transwell assays, we showed LINC00339 knockdown suppressed GC cell proliferation, migration, and invasion in vitro. Flow cytometry analysis (FACS) indicated that LINC00339 knockdown induced tumor cell apoptosis. Besides, we utilized the xenograft assay and found that LINC00339 depletion led to decreased tumor growth in vivo. Mechanistically, miR-377-3p was found to be inhibited by LINC00339. And LINC00339 suppressed miR-377-3p to upregulate DCP1A, which consequently promoted GC progression. In conclusion, LINC00339 promotes gastric cancer progression by elevating DCP1A expression via inhibiting miR-377-3p.     

LINC00052 functions as a tumor suppressor through negatively modulating miR-330-3p in pancreatic cancer

Pancreatic cancer is a serious solid malignant tumor worldwide. Increasing evidence has pointed out that abnormal expressions of long noncoding RNAs are involved in various tumors. Meanwhile, LINC00052 is reported as a famous tumor regulator in several cancers. Nevertheless, the biological role of LINC00052 in pancreatic cancer progression is still unknown. Our study was to explore the specific mechanism of LINC00052 in pancreatic cancer. First, we observed that the LINC00052 was obviously downregulated in several pancreatic cancer cell lines. Overexpression of LINC00052 greatly repressed AsPC-1 and SW1990 cell proliferation, triggered the apoptosis and prevented cell cycle in the G1 phase. For another, AsPC-1 and SW1990 cell migration and invasion capacity were also obviously repressed by LINC00052 upregulation. Moreover, miR-330-3p was elevated in pancreatic cancer cells and can function as a target of LINC00052 confirmed by luciferase reporter and RNA Immunoprecipitation (RIP) experiments. Inhibition of miR-330-3p could depress pancreatic cancer progression while overexpressed miR-330-3p exhibited an opposite process. Finally, our data indicated that the LINC00052 also remarkably suppressed pancreatic tumor growth via modulating miR-330-3p in vivo. To conclude, our study revealed that the LINC00052 might provide a new perspective for pancreatic cancer therapy.