Long non‐coding RNA SNHG15 promotes CDK14 expression via miR‐486 to accelerate non‐small cell lung cancer cells progression and metastasis

Long non‐coding RNAs (lncRNAs) have been validated to play important role in multiple cancers, including non‐small cell lung cancer (NSCLC). In present study, our team investigate the biologic role of SNHG15 in the NSCLC tumorigenesis. LncRNA SNHG15 was significantly upregulated in NSCLC tissue samples and cells, and its overexpression was associated with poor prognosis of NSCLC patients. In vitro, loss‐of‐functional cellular experiments showed that SNHG15 silencing significantly inhibited the proliferation, promoted the apoptosis, and induced the cycle arrest at G0//G1 phase. In vivo, xenograft assay showed that SNHG15 silencing suppressed tumor growth of NSCLC cells. Besides, SNHG15 silencing decreased CDK14 protein expression both in vivo and vitro. Bioinformatics tools and luciferase reporter assay confirmed that miR‐486 both targeted the 3′‐UTR of SNHG15 and CDK14 and was negatively correlated with their expression levels. In summary, our study conclude that the ectopic overexpression of SNHG15 contribute to the NSCLC tumorigenesis by regulating CDK14 protein via sponging miR‐486, providing a novel insight for NSCLC pathogenesis and potential therapeutic strategy for NSCLC patients.     

LINC01303 functions as a competing endogenous RNA to regulate EZH2 expression by sponging miR‐101‐3p in gastric cancer

Long non‐coding RNA (lncRNA) is one of the important regulators of many malignancies. However, the biological function and clinical significance of a large number of lncRNAs in gastric cancer remain unclear. Therefore, we analysed the TCGA data to find that LINC01303 is significantly up‐regulated in gastric cancer tissues. However, the biological function of LINC01303 in GC remains unknown. In our study, we found that the expression of LINC01303 was significantly higher in GC tissues than in adjacent tissues by real‐time quantitative PCR. We can significantly inhibit the malignant proliferation, migration and invasion of GC cells by silencing LINC01303 expression. In addition, LINC01303 knockdown can also inhibit GC growth in vivo. After the bioinformatics analysis, we found that LINC01303 can be used as a miR‐101‐3p sponge to competitively adsorb miR‐101‐3p with EZH2. Therefore, our results indicate that LINC01303 promotes the expression of EZH2 by inhibiting miR‐101‐3p activity and promotes GC progression. In summary, in this study, we demonstrated for the first time that the LINC01303/miR‐101‐3p/EZH2 axis promotes GC progression.     

Long non‐coding RNA SNHG16 regulates human aortic smooth muscle cell proliferation and migration via sponging miR‐205 and modulating Smad2

The present study investigated the role of long non‐coding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) in the human aortic smooth muscle cell (HASMC) proliferation and migration and explored the potential link between SNHG16 and atherosclerosis. Our results showed that platelet‐derived growth factor (PDGF)‐bb treatment promoted cell proliferation and migration with concurrent up‐regulation of SNHG16 in HASMCs. Small nucleolar RNA host gene 16 overexpression promoted HASMC proliferation and migration, while SNHG16 knockdown suppressed cell proliferation and migration in PDGF‐bb‐stimulated HASMCs. The bioinformatic analyses showed that SNHG16 possessed the complementary binding sequence with miR‐205, where the interaction was confirmed by luciferase reporter assay and RNA pull‐down assay in HASMCs, and SNHG16 inversely regulated miR‐205 expression. MiR‐205 overexpression attenuated the enhanced effects of PDGF‐bb treatment on HASMC proliferation and migration. Moreover, Smad2 was targeted and inversely regulated by miR‐205, while being positively regulated by SNHG16 in HASMCs. Smad2 knockdown attenuated PDGF‐bb‐mediated actions on HASMC proliferation and migration. Both miR‐205 overexpression and Smad2 knockdown partially reversed the effects of SNHG16 overexpression on HASMC proliferation and migration. Moreover, SNHG16 and Smad2 mRNA were up‐regulated, while miR‐205 was down‐regulated in the plasma from patients with atherosclerosis. Small nucleolar RNA host gene 16 expression was inversely correlated with miR‐205 expression and positively correlated with Smad2 expression in the plasma from atherosclerotic patients. In conclusion, our data showed the up‐regulation of SNHG16 in pathogenic‐stimulated HASMCs and clinical samples from atherosclerotic patients. Small nucleolar RNA host gene 16 regulated HASMC proliferation and migration possibly via regulating Smad2 expression by acting as a competing endogenous RNA for miR‐205.     

Long noncoding RNA WDFY3-AS2 suppresses tumor progression by acting as a competing endogenous RNA of microRNA-18a in ovarian cancer

Ovarian cancer (OC) is a fatal cancer in women, mainly due to its aggressive nature and poor survival rate. The lncRNA-miRNA-mRNA (long noncoding RNA-microRNA-messenger RNA) interaction is promising biomarkers for the improving prognosis of OC. Therefore, we explored the regulatory mechanism of WDFY3-AS2/miR-18a/RORA axis involved in the biological activities of OC cells. Microarray analysis predicted differentially expressed lncRNA, miRNA, and mRNA related to OC, followed by investigating the relationship among them. The expression patterns of the identified lncRNA WDFY3-AS2, miR-18a, and RORA were measured in OC tissue and cells. Gain- and loss-of-function experiments were performed to characterize the effect of lncRNA WDFY3-AS2 on OC cells, as well as the involvement of miR-18a and RAR related orphan receptor A (RORA). The in vitro assays were validated by in vivo experiments. According to bioinformatics analysis, WDFY3-AS2 was speculated to affect OC by sponging miR-18a and modulating RORA. WDFY3-AS2 and RORA were underexpressed in OC, while miR-18a was highly expressed. Notably, WDFY3-AS2 acts as a competing endogenous RNA to sponge miR-18a and upregulate RORA. Upon overexpressing WDFY3-AS2 or inhibiting miR-18a, RORA expression was increased, thereby the OC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) were suppressed, accompanied by enhanced apoptosis. In vivo experiments confirmed that the tumor growth was reduced in response to overexpressed WDFY3-AS2 or inhibited miR-18a. Taken together, the lncRNA WDFY3-AS2/miR-18a axis regulates the tumor progression of OC by targeting RORA, providing new insights for prevention and control of OC.     

LncRNA SNHG1 exerts a protective role in cardiomyocytes hypertrophy via targeting miR‐15a‐5p/HMGA1 axis

Heart failure preceded by pathological cardiac hypertrophy is a leading cause of death. Long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) was reported to inhibit cardiomyocytes apoptosis, but the role and underlying mechanism of SNHG1 in pathological cardiac hypertrophy have not yet been understood. This study was designed to investigate the role and molecular mechanism of SNHG1 in regulating cardiac hypertrophy. We found that SNHG1 was upregulated during cardiac hypertrophy both in vivo (transverse aortic constriction treatment) and in vitro (phenylephrine [PE] treatment). SNHG1 overexpression attenuated the cardiomyocytes hypertrophy induced by PE, while SNHG1 inhibition promoted hypertrophic response of cardiomyocytes. Furthermore, SNHG1 and high‐mobility group AT‐hook 1 (HMGA1) were confirmed to be targets of miR‐15a‐5p. SNHG1 promoted HMGA1 expression by sponging miR‐15a‐5p, eventually attenuating cardiomyocytes hypertrophy. There data revealed a novel protective mechanism of SNHG1 in cardiomyocytes hypertrophy. Thus, targeting of SNHG1‐related pathway may be therapeutically harnessed to treat cardiac hypertrophy.     

Long non‐coding RNA SNHG6 promotes cell proliferation and migration through sponging miR‐4465 in ovarian clear cell carcinoma

Dysregulation of small nucleolar RNA host gene 6 (SNHG6) exerts critical oncogenic effects and facilitates tumourigenesis in human cancers. However, little information about the expression pattern of SNHG6 in ovarian clear cell carcinoma (OCCC) is available, and the contributions of this long non‐coding RNA to the tumourigenesis and progression of OCCC are unclear. In the present study, we showed via quantitative real‐time PCR that SNHG6 expression was abnormally up‐regulated in OCCC tissues relative to that in unpaired normal ovarian tissues. High SNHG6 expression was correlated with vascular invasion, distant metastasis and poor survival. Further functional experiments demonstrated that knockdown of SNHG6 in OCCC cells inhibited cell proliferation, migration and invasion in vitro as well as tumour growth in vivo. Moreover, SNHG6 functioned as a competing endogenous RNA (ceRNA), effectively acting as a sponge for miR‐4465 and thereby modulating the expression of enhancer of zeste homolog 2 (EZH2). Taken together, our data suggest that SNHG6 is a novel molecule involved in OCCC progression and that targeting the ceRNA network involving SNHG6 may be a treatment strategy in OCCC.     

Long non‐coding RNA SNHG20 promotes the tumorigenesis of oral squamous cell carcinoma via targeting miR‐197/LIN28 axis

Long non‐coding RNA (lncRNA) has been verified to participate in the tumour regulation, including oral squamous cell carcinoma (OSCC). Nevertheless, the role of lncRNA SNHG20 on OSCC still remains elusive. Here, we investigate the physiopathologic functions of lncRNA SNHG20 in OSCC tumorigenesis and explore its potential mechanism. LncRNA SNHG20 was up‐regulated in OSCC tissue compared with adjacent non‐tumour tissue. Meanwhile, SNHG20 was overexpressed in cancer stem‐like cells. In vitro and in vivo, loss‐of‐function experiments showed that lncRNA SNHG20 knockdown inhibited proliferative ability, mammosphere‐forming ability, ALDH1 expression, stem factors (LIN28, Nanog, Oct4, SOX2) and tumour growth. Bioinformatics and luciferase reporter assay revealed that miR‐197 targeted the 3′‐untranslated regions of SNHG20 and LIN28 by complementary binding. Validation experiments confirmed the associated functions of SNHG20/miR‐197/LIN28 axis on OSCC proliferation and stemness. In summary, our results reveal the important function of SNHG20/miR‐197/LIN28 axis in the oncogenesis and stemness of OSCC, suggesting the vital role of SNHG20 in OSCC tumorigenesis.     

LncRNA NR2F2‐AS1 promotes tumourigenesis through modulating BMI1 expression by targeting miR‐320b in non‐small cell lung cancer

Recently, long noncoding RNAs (lncRNAs) are attracting wide attention in the field of cancer research because of its important role in cancer diagnosis and prognosis. But studies on the biological effects and relevant mechanisms of lncRNAs in non‐small cell lung cancer (NSCLC) remain few and need to be enriched. Our study discussed the expression and biological effects of LncRNA NR2F2‐AS1, and further explored its possible molecular mechanisms. As a result, elevated expression of NR2F2‐AS1 was detected in NSCLC tissues and cells and was remarkably associated with the tumor, node, metastasis (TNM) stage and the status of lymphatic metastasis of patients. Down‐regulated NR2F2‐AS1 contributed to the promotion of cell apoptosis and the inhibition of cell proliferation and invasion in A549 and SPC‐A‐1 cells in vivo and vitro. Through bioinformatics analysis, NR2F2‐AS1 functions as a ceRNA directly binding to miR‐320b, BMI1 was a direct target of miR‐320b. Combined with the following cellular experiments, the data showed that NR2F2‐AS1 may influence the NSCLC cell proliferation, invasion and apoptosis through regulating miR‐320b targeting BMI1.     

LncRNA SNHG6 functions as a ceRNA to regulate neuronal cell apoptosis by modulating miR‐181c‐5p/BIM signalling in ischaemic stroke

Long non‐coding RNAs (lncRNAs) play important roles in the pathogenesis of brain and neurodegenerative disorders. As far as we know, the functions and potential mechanisms of small nucleolar RNA host gene 6 (SNHG6) in ischaemic stroke have not been explored. This study aimed to examine the functional role of SNHG6 in the ischaemic stroke. Middle cerebral artery occlusion (MCAO) in mice and the oxygen glucose deprivation (OGD)‐induced injury in neuronal cells were applied to mimic ischaemic stroke. TTC staining, quantitative real‐time PCR, cell apoptosis assay, caspase‐3 activity assay, Western blot, RNA immunoprecipitation and luciferase reporter assay were performed to evaluate the function and possible mechanisms of SNHG6 in the pathogenesis of ischaemic stroke. The results show that SNHG6 expression was significantly increased both OGD‐induced neuronal cells and MCAO model mice. In vitro results showed that inhibition of SNHG6 increased cell viability, inhibited cell apoptosis and caspase‐3 activity in OGD‐induced neuronal cells. Consistently, knockdown of SNHG6 reduced brain infarct size and improved neurological scores in the MCAO mice. Mechanistic study further revealed that SNHG6 functioned as a competing endogenous RNA (ceRNA) for miR‐181c‐5p, which in turn repressed its downstream target of Bcl‐2 interacting mediator of cell death (BIM) and inhibiting cell apoptosis. This study revealed a novel function of SNHG6 in the modulating neuronal apoptosis in the ischaemic stroke model, and the role of SNHG6 in the regulating of neuronal apoptosis was at least partly via targeting miR‐181c‐5p/BIM signalling pathway.     

miR‐4732‐5p promotes breast cancer progression by targeting TSPAN13

MiR‐4732‐5p was previously found to be dysregulated in nipple discharge of breast cancer. However, the expression and function of miR‐4732‐5p in breast cancer remain largely unknown. Here, the expression of miR‐4732‐5p was detected using quantitative real‐time PCR in breast cancer tissues and cell lines. Cell proliferation, apoptosis, migration and invasion assays were performed to examine the effects of miR‐4732‐5p in breast cancer. In addition, mRNA sequencing, bioinformatics analysis, Western blot and luciferase assays were performed to identify the target of miR‐4732‐5p. Overall, miR‐4732‐5p was significantly down‐regulated in breast cancer tissues, especially in lymph node metastasis (LNM)‐negative tissues, compared with adjacent normal tissues. However, it was more highly expressed in LNM‐positive breast cancer tissues, compared with LNM‐negative ones. Expression of miR‐4732‐5p was positively correlated with lymph node metastasis, larger tumour size, advanced clinical stage, high Ki‐67 levels and poor prognosis. MiR‐4732‐5p promoted cell proliferation, migration and invasion in breast cancer. MiR‐4732‐5p directly targeted the 3′‐UTR of tetraspanin 13 (TSPAN13) and suppressed TSPAN13 expression at the mRNA and protein levels. These results suggested that miR‐4732‐5p may serve as a tumour suppressor in the initiation of breast cancer, but as a tumour promoter in breast cancer progression by targeting TSPAN13.