Linc01133 contributes to gastric cancer growth by enhancing YES1-dependent YAP1 nuclear translocation via sponging miR-145-5p

The long intergenic non-coding RNA linc01133 is reported to be oncogenic in various malignancies. However, the role and mechanism of linc01133 in regulating gastric cancer growth is still not clear. In the present study, we found that linc01133 was significantly upregulated in gastric cancer tissues compared to non-tumorous gastric tissues. Linc01133 over-expression significantly correlated with tumor size and tumor differentiation in gastric cancer patients. The expression of linc01133 was regulated by c-Jun and c-Fos collaboratively. In both in vitro and in vivo studies, linc01133 was shown to promote gastric cancer cell growth. Linc01133 localized in the cytoplasm and functioned as an endogenous competing RNA of miR-145-5p to upregulate the expression of YES1, which was proved to be the target gene of miR-145-5p. By promoting YES1-dependent YAP1 nuclear translocation, linc01133 upregulated the expression of the key cell cycle regulators CDK4, CDK6 and cyclin D1 to promote G1-S phase transition. Thus, our study unveiled the function and mechanism of linc01133 regulating cell cycle progression in gastric cancer.Subject terms: Gastric cancer, Cell growth     

Long noncoding RNA linc00467 plays an oncogenic role in hepatocellular carcinoma by regulating the miR-18a-5p/NEDD9 axis

Increasing evidence has shown that numerous long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis. Herein, we investigated the biological role of lncRNA linc00467 in the cancer biology of hepatocellular carcinoma (HCC). We observed that linc00467 was upregulated in HCC tissues and cells. Silencing of linc00467 using small interfering RNA interference significantly inhibited the growth and motility of HCC cells, and increased cell apoptosis through regulating the Bcl-2/Bax axis and the caspase cascade, suggesting that linc00467 exerted oncogenic functions in the progression of HCC. Moreover, we found that linc00467 could target miR-18a-5p, and NEDD9 was a target for miR-18a-5p in HCC cells. Furthermore, either the miR-18a-5p inhibitor or upregulation of NEDD9 could recover the inhibitory effects caused by silencing of linc00467. In conclusion, our data highlighted the oncogenic role of linc00467 in HCC progression by regulating the miR-18a-5p/NEDD9 axis.     

LncRNA BLACAT1 regulates VASP expression via binding to miR-605-3p and promotes giloma development

Glioma, an aggressive tumor in brain, presents a very poor prognosis. Emerging evidence has demonstrated that dysfunction of long noncoding RNAs (lncRNAs) is closely related to giloma development. However, the roles of lncRNA BLACAT1 in glioma are not unknown. In this study, we utilized in vitro and in vivo experiments to explore the effects of BLACAT1 on glioma cells. BLACAT1 levels were increased in glioma tissues. Upregulation of BLACAT1 showed poor prognosis. Silencing of BLACAT1 markedly repressed glioma proliferation, migration, and invasion, and suppressed glioma growth in vivo. We also illustrated that BLACAT1 worked as the sponge for miR-605-3p and promoted VASP expression. miR-605-3p was downregulated in glioma and repressed glioma proliferation, migration, and invasion. And VASP is upregulated and contributed to glioma progression. Summarily, this study highlights the important roles of BLACAT1/miR-605-3p/VASP axis in glioma progression.     

MiR-508-5p Inhibits the Progression of Glioma by Targeting Glycoprotein Non-metastatic Melanoma B

Glioma is a severe and highly lethal brain cancer, a malignancy largely stemming from growing in a relatively restrained area of the brain. Hence, the understanding of the molecular regulation of the growth of glioma is critical for improving its treatment. MicroRNA has become a hotspot in research on diseases, especially in the initiation and progression of different types of cancer. However, the molecular function and mechanisms of miR-508-5p in gliomagenesis are still unclear. The aim of this study was to investigate miR-508-5p expression in glioma and determine its effects on proliferation. miR-508-5p expression levels, both in glioma cell lines and in tissue, were significantly lower than in a normal human astrocyte cell line or adjacent tissues. Cell growth was analyzed using a MTT assay and over-expression of miR-508-5p was found to decrease glioma cell growth. Moreover, a bioinformatic analysis was performed, showing that glycoprotein non-metastatic melanoma B (GPNMB) was a direct target for miR-508-5p in glioma cells. Furthermore, in vivo treatment with miR-508-5p reduced GPNMB protein levels in the tumor. Additionally, overexpression of GPNMB without 3′-UTR partially reversed the cell growth arrest induced by miR-508-5p over-expression in glioma cells. In conclusion, these results indicate that increased expression of miR-508-5p might be related to glioma progression, indicating a potential role of miR-508-5p for clinical therapy.     

MiR-483-5p suppresses the proliferation of glioma cells via directly targeting ERK1

MicroRNAs (miRNAs) exhibit tumor-specific expression signatures and play crucial roles in tumorigenesis by targeting oncogenes. Here, through analyzing the miRNA-array profiles of human glioblastoma tissues and the adjacent normal brain tissues, we found miR-483-5p was significantly down-regulated in gliomas, which was confirmed in both human glioma specimens and cell lines. The overexpression of miR-483-5p suppressed glioma cell proliferation and induced a G0/G1 arrest. In contrast, miR-483-5p inhibition promoted cell proliferation. Furthermore, by a dual-luciferase reporter assay and expression analysis, we identified extracellular signal-regulated kinase 1 (ERK1) as a direct target of miR-483-5p. ERK1 knockdown can block cell proliferation induced by miR-483-5p inhibition. Thus, our findings provide the first evidence that miR-483-5p can serve as a tumor suppressor in gliomas.     

lncRNA NEAT1 facilitates melanoma cell proliferation,migration, and invasion via regulating miR-495-3p and E2F3

Melanoma contributes a lot to skin cancer-related deaths. lncRNAs are implicated in various diseases, including melanoma. lncRNA NEAT1 is frequently dysregulated and can play important roles in multiple cancers. Nevertheless, little has been studied about the function of NEAT1 in melanoma progression. In our present research, we displayed NEAT1 was overexpressed in melanoma cells. A series of functional assays showed that overexpression of NEAT1 promoted the proliferation, migration, and invasion of melanoma cells. By contrast, NEAT1 knockdown obviously restrained melanoma cell progression. Mechanistically, it was revealed that NEAT1 could directly bind with miR-495-3p, which led to a negative effect on miR-495-3p levels. In addition, miR-495-3p was significantly decreased in melanoma cells. Furthermore, E2F3 was postulated as the target of miR-495-3p and overexpression of this miR could suppress the levels of E2F3. Meanwhile, it was exhibited that melanoma cell proliferation, migration, and invasion induced by E2F3 silence was abrogated by miR-495-3p. Moreover, an in vivo xenograft nude mice model was established using A375 cells and it was indicated that NEAT1 promoted melanoma progression in vivo via regulating the miR-495-3p/E2F3 axis. In conclusion, we suggest that NEAT1 exerts an oncogenic effect on melanoma development via inhibition of miR-495-3p and induction of E2F3. NEAT1 might serve as a crucial prognostic biomarker of melanoma.     

miR-376a inhibits glioma proliferation and angiogenesis by regulating YAP1/VEGF signalling via targeting of SIRT1

BackgroundGlioma is the most common cancer in the central nervous system. Previous studies have revealed that the miR-376 family is crucial in tumour development; however, its detailed mechanism in glioma is not clear.MethodsCellular mRNA or protein levels of miR-376a, SIRT1, VEGF and YAP1 were detected via qRT–PCR or Western blotting. We analysed the proliferation, angiogenesis and migration abilities of glioma cell lines using colony formation, tube formation and Transwell assays. A luciferase assay was performed to determine whether miR-376a could recognize SIRT1 mRNA. Xenograft experiments were performed to analyse the tumorigenesis capacity of glioma cell lines in nude mice. The angiogenesis marker CD31 in xenograft tumours was detected via immunohistochemistry (IHC).ResultsmiR-376a expression was lower in glioma cells than in normal astrocytes. miR-376a mimic inhibited SIRT1, YAP1, and VEGF expression and suppressed the proliferation, migration and angiogenesis abilities of the glioma cell lines LN229 and A172, whereas miR-376a inhibitor exerted the opposite functions. In a luciferase assay, miR-376a inhibited the luciferase activity of WT-SIRT1. SIRT1 overexpression upregulated YAP1 and VEGF in glioma cells and promoted proliferation, migration and angiogenesis. Xenografts with ectopic miR-376a expression exhibited lower volumes and weights and a slower growth curve. Overexpression of miR-376a inhibited YAP1/VEGF signalling and angiogenesis by inhibiting SIRT1 in xenograft tissues.ConclusionmiR-376a directly targets and inhibits SIRT1 in glioma cells. Downregulation of SIRT1 resulted in decreased YAP1 and VEGF signalling, which led to suppression of glioma cell proliferation, migration and angiogenesis.     

MicroRNA-628-5p inhibits cell proliferation in glioma by targeting DDX59

Recent study has reported that microRNA-628-5p (miR-628-5p) is involved in the development of epithelial ovarian cancer; however, the mechanisms of miR-628-5p in glioma remain unclear. In this study, we explored the potential biological roles of miR-628-5p in glioma. First, we found that miR-628-5p was decreased in the tissues and cells (U87 and T98) of glioma. Second, overexpressing miR-628-5p reduced the ability of glioma cells' proliferation and induced glioma cells' cycle arrest in G1. Then, we found that miR-628-5p directly bound to the 3′-untranslated region of DDX59 and decreased the protein level of DDX59. The decrease of DDX59 was found to lead to the decrease of p-AKT. Mechanistic studies revealed that restoring the expression of DDX59 alleviated miR-628-5p-induced inhibition of proliferation of glioma. These findings suggest that the miR-628-5p/DDX59 axis has a key role in the development of glioma, and miR-628-5p might be a new therapeutic target against glioma.     

Long noncoding RNA FLVCR1-AS1 aggravates biological behaviors of glioma cells via targeting miR-4731-5p/E2F2 axis

Long noncoding RNAs (lncRNAs) display essential roles in cancer progression. FLVCR1-AS1 is a rarely investigated lncRNAs involved in various human cancers, such as hepatocellular carcinoma and lung cancer. However, its function in glioma has not been clarified. In our study, we found that FLVCR1-AS1 was highly expressed in glioma tissues and cell lines. And upregulation of FLVCR1-AS1 predicted poor prognosis in patients with glioma. Moreover, FLVCR1-AS1 knockdown inhibited proliferation, migration and invasion of glioma cells. Through bioinformatics analysis, we identified that FLVCR1-AS1 was a sponge for miR-4731-5p to upregulate E2F2 expression. Moreover, rescue assays indicated that FLVCR1-AS1 modulated E2F2 expression to participate in glioma progression. Altogether, our research demonstrates that the FLVCR1-AS1/miR-4731-5p/E2F2 axis is a novel signaling in glioma and may be a potential target for tumor therapy.     

Long non‐coding RNA linc00261 suppresses gastric cancer progression via promoting Slug degradation

Gastric cancer (GC) remains a threat to public health with high incidence and mortality worldwide. Increasing evidence demonstrates that long non‐coding RNAs (lncRNAs) play critical regulatory roles in cancer biology, including GC. Previous profiling study showed that lncRNA linc00261 was aberrantly expressed in GC. However, the role of linc00261 in GC progression and the precise molecular mechanism remain unknown. In this study, we report that linc00261 was significantly down‐regulated in GC tissues and the expression level of linc00261 negatively correlated with advanced tumour status and clinical stage as well as poor prognostic outcome. In vitro functional assays indicate that ectopic expression of linc00261 suppressed cell invasion by inhibiting the epithelial–mesenchymal transition (EMT). By RNA pull‐down and mass spectrum experiments, we identified Slug as an RNA‐binding protein that binds to linc00261. We confirmed that linc00261 down‐regulated Slug by decreasing the stability of Slug proteins and that the tumour‐suppressive function of linc00261 can be neutralized by Slug. linc00261 may promote the degradation of Slug via enhancing the interaction between GSK3β and Slug. Moreover, linc00216 overexpression repressed lung metastasis in vivo. Together, our findings suggest that linc00261 acts a tumour suppressor in GC by decreasing the stability of Slug proteins and suppressing EMT. By clarifying the mechanisms underlying GC progression, these findings may facilitate the development of novel therapeutic strategies for GC.     

The long noncoding RNA ZFAS1 promotes the progression of glioma by regulating the miR-150-5p/PLP2 axis

Numerous studies have reported that long noncoding RNA (lncRNA) dysregulation is involved in the progression of many malignant tumors, including glioma. The lncRNA ZNFX1 antisense RNA 1 (ZFAS1) plays an oncogenic role in various malignant tumors, such as gastric cancer and hepatocellular carcinoma. However, the underlying molecular mechanism of ZFAS1 in glioma has not been fully clarified. In this study, we found that the expression of ZFAS1 was upregulated in both glioma tissues and cell lines. Functional experiments revealed that ZFAS1 promoted glioma proliferation, migration and invasion, and increased resistance to temozolomide in vitro. By using online databases, RNA pull-down assays and luciferase reporter assays, ZFAS1 was demonstrated to act as a sponge of miR-150-5p. Furthermore, proteolipid protein 2 (PLP2) was shown to be the functional target of miR-150-5p. Rescue experiments revealed that ZFAS1 regulated the expression of PLP2 by sponging miR-150-5p. Finally, a xenograft tumor assay demonstrated that ZFAS1 promoted glioma growth in vivo. Our results showed that ZFAS1 promoted glioma malignant progression by regulating the miR-150-5p/PLP2 axis, which may provide a potential therapeutic target for the treatment of glioma.     

MiRNA-139–3p inhibits the proliferation,invasion, and migration of human glioma cells by targeting MDA-9/syntenin

Gliomas are the most common primary malignant brain tumor in adults. Although these tumors are aggressive and frequently lethal, there are currently few therapeutic approaches available to prolong patient survival. MicroRNAs play important roles in regulating the expression of genes that control diverse cellular processes. Here, we investigated the expression and function of miR-139–3p in gliomas using clinical specimens, cultured cells, and a mouse xenograft tumor model. We found that miR-139–3p expression is markedly lower in human glioma tissues than in normal brain tissues. We identified melanoma differentiation-associated gene-9 (MDA-9)/syntenin, an adaptor protein implicated in tumor metastasis, as a novel direct target of miR-139–3p and showed that syntenin mRNA and miR-139–3p levels were inversely correlated in clinical specimens (r?=??0.6817, P?=?0.0002). Overexpression of miR-139–3p in human glioma cell lines inhibited cell proliferation, migration, and invasion, and these effects were rescued by co-transfection with syntenin. Our results indicate that miR-139–3p plays a significant role in controlling behaviors associated with the malignant progression of gliomas, and we identify the miR-139-3p–syntenin axis as a potential therapeutic target for glioma.     

MiR-375-3p alleviates the severity of inflammation through targeting YAP1/LEKTI pathway in HaCaT cells

ABSTRACT

Atopic dermatitis (AD) is a relapsing inflammatory skin disease with a complicated pathogenesis. This study aimed to investigate whether miR-375-3p could regulate AD through the Yes-associated protein 1 (YAP1) pathway. In this study, inflammatory response was induced by TNF-α and IFN-γ administration in HaCaT cells. We found that viability and inflammatory factor release, including interleukin-1β (IL-1β) and IL-6, were negatively related to miR-375-3p expression in HaCaT cells. We also found that YAP1 overexpression down-regulated lympho-epithelial Kazal type inhibitor (LEKTI) levels and aggravated viability and inflammation in TNF-α and IFN-γ-treated HaCaT cells. Dual-luciferase reporter assay proved the targeted binding of miR-375-3p and YAP1 3?-UTR. Additionally, the protective effect of miR-375-3p on inflammatory response in TNF-α and IFN-γ-treated HaCaT cells could be impeded by YAP1 overexpression. Collectively, our results suggested that miR-375-3p could modulate HaCaT cell viability and inflammation through the YAP1/LEKTI pathway.