Overexpression of long non-coding RNA RP11-363E7.4 inhibits proliferation and invasion in gastric cancer

LncRNA RP11-363E7.4 has been shown to be downregulated in gastric cancer (GC), while the effect of lncRNA RP11-363E7.4 on GC and its potential molecular mechanisms is unclear. The purpose of this study was to explore the functional role and underlying molecular mechanisms of lncRNA RP11-363E7.4 involved in GC progress.To address the question, quantitative real-time PCR assay was performed to confirm lncRNA RP11-363E7.4 expression levels in GC tissues and cell lines. Cell proliferation, apoptosis, migration and invasion were estimated using Cell Counting Kit-8, colony formation, scratch wound healing and Transwell assays. Potential molecular mechanisms were evaluated using western blot assay. The results showed that lncRNA RP11-363E7.4 was significantly downregulated in GC cell lines and 82 paired tissues. The correlation between expression and clinicopathological features indicated that low expression of lncRNA RP11-363E7.4 was associated with T stage (P = .010). Functional experiments showed that overexpression of lncRNA RP11-363E7.4 prevented proliferation, migration, and invasion and induced apoptosis of GC cells. Western blot assay revealed that lncRNA RP11-363E7.4 functioned via the p53, Bax/Bcl-2, β-catenin pathway. In summary, this study revealed that lncRNA RP11-363E7.4 functioned as a tumour suppressor by inhibiting proliferation, migration, and invasion and inducing apoptosis of GC cells. Significance of the study :LncRNA RP11-363E7.4 has been shown to be downregulated in GC, while the effect of lncRNA RP11-363E7.4 on GC and its potential molecular mechanism is unclear. We revealed that lncRNA RP11-363E7.4 functioned as a tumour suppressor by inhibiting proliferation, migration, and invasion and inducing apoptosis of GC cells. LncRNA RP11-363E7.4 might become an attractive diagnostic and prognostic biomarker of GC and a promising target for GC treatment.     

MiR-126-3p inhibits ovarian cancer proliferation and invasion via targeting PLXNB2

Ovarian cancer is one of the leading malignancies in women and the 5-year survival rate of ovarian cancer still remains poor. In the present study, we aimed to investigate the interaction between the miR-126-3p and PLXNB2 in the progression of ovarian cancer. The qRT-PCR data revealed a reduction of miR-126-3p level in ovarian cancer tissues comparing to the adjacent normal tissues. Over-expression of miR-126-3p in ovarian cancer cells suppressed cell proliferation and invasion and the phosphorylation of AKT and ERK1/2. The cell cycle assay results showed that the over-expression of miR-126-3p induced cells in G1-phase and reduced cells in S-phase. We further performed bioinformatics analysis and luciferase assay to investigate the relationship between miR-126-3p and PLXNB2 in ovarian cancer cells. The results of TargetScan suggested that PLXNB2 is a direct target of miR-126-3p in ovarian cancer cells, and luciferase assay confirmed bioinformatics prediction. Knocking down of PLXNB2 with PLXNB2 siRNA results in repressed ovarian cancer cell proliferation and invasion, and decreased phosphorylation of AKT and ERK1/2, which is similar to the effect of over-expression of miR-126-3p in OC cells. The synergistic effect of combination of miR-126-3p over-expression and PLXNB2 down-regulation on the cell growth viability, cell colony, and cell invasion was also identified. All these findings indicated that miR-126-3p is involved in the progression of ovarian cancer via direct regulating PLXNB2.     

Long non-coding RNA LINC00460 promotes proliferation and inhibits apoptosis of cervical cancer cells by targeting microRNA-503-5p

Molecular and Cellular Biochemistry - We reported previously that the rat submandibular gland is able to release nanovesicles capable to hydrolyse millimolar concentrations of ATP, ADP and AMP in...     

Long non-coding RNA PRNCR1 promotes ovarian cancer cell proliferation,migration and invasion by targeting the miR-653-5p/ELF2 axis

Molecular and Cellular Biochemistry - Recent studies have shown that prostate cancer-associated long non-coding RNA, PRNCR1, plays crucial roles in the development of multiple human cancers....     

MicroRNA-409-3p inhibits migration and invasion of bladder cancer cells via targeting c-Met

There is increasing evidence suggesting that dysregulation of certain microRNAs (miRNAs) may contribute to tumor progression and metastasis. Previous studies have shown that miR-409-3p is dysregulated in some malignancies, but its role in bladder cancer is still unknown. Here, we find that miR-409-3p is down-regulated in human bladder cancer tissues and cell lines. Enforced expression of miR-409-3p in bladder cancer cells significantly reduced their migration and invasion without affecting cell viability. Bioinformatics analysis identified the pro-metastatic gene c-Met as a potential miR-409-3p target. Further studies indicated that miR-409-3p suppressed the expression of c-Met by binding to its 3′-untranslated region. Silencing of c-Met by small interfering RNAs phenocopied the effects of miR-409-3p overexpression, whereas restoration of c-Met in bladder cancer cells bladder cancer cells overexpressing miR-409-3p, partially reversed the suppressive effects of miR-409-3p. We further showed that MMP2 and MMP9 may be downstream effector proteins of miR-409-3p. These findings indicate that miR-409-3p could be a potential tumor suppressor in bladder cancer.     

长链非编码RNA AFAP1-AS1促进肿瘤侵袭转移

<正>人类基因组计划及其后续的DNA元件百科全书计划(The Encyclopedia of DNA Elements Project,ENCODE)研究成果表明,蛋白质编码基因序列仅占人类基因组序列的1%~3%,人基因组中绝大部分可转录的序列为长链非编码RNA(long non-coding RNA,lnc RNAs)[1].Lnc RNA广泛地存在于各种生物中,且随着生物复杂程度的升高,基因组中lnc RNA序列的比例也相应地增大,提示lnc RNA在生物进化过程中可能有着重要意义[2-4].随着     

miR-377-5p inhibits lung cancer cell proliferation,invasion, and cell cycle progression by targeting AKT1 signaling

Lung carcinoma is the most common type of malignant tumors globally, and its molecular mechanisms remained unclear. With the aim to investigate the effects of microRNA (miR)-377-5p on the cell development, invasion, metastasis, and cycle of lung carcinoma, this study was performed. We evaluated miR-377-5p expression levels in lung cancer tissues and cell models. Cell viability, proliferation, migration, invasion abilities, and cell cycle distribution were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, crystal violet, transwell, and flow cytometry assay. Furthermore, expression levels of protein kinase B α subunit (AKT1) and proteins related to cell cycle and epithelial-mesenchymal transition (EMT) were assessed using Western blot analysis and quantitative real-time polymerase chain reaction. These results suggested that miR-377-5p was downregulated in vivo and in cell models, and miR-377-5p overexpression inhibited cell viability, proliferation, migration, invasion, and induced cell-cycle arrest. In addition, as a target of miR-377-5p, AKT1 alleviated the decreases of cell viability, proliferation, migration, invasion, the S-phase cells, the expression of cyclin D1, fibronectin, and vimentin, as well as the increases of the G0/G1-phase cells, the expression of Foxo1, p27 ^kip1, p21 ^Cip1 and E-cadherin when miR-377-5p overexpressed. In conclusion, miR-377-5p inhibited cell development and regulated cell cycle distribution and EMT by targeting AKT1, which provided a theoretical basis for further study of lung carcinoma therapeutics.     

MicroRNA-221 promotes colorectal cancer cell invasion and metastasis by targeting RECK

MicroRNAs (miRNAs) have recently emerged as regulators of metastasis. We provide insight into the behavior of miR-221 in colorectal cancer (CRC) metastasis by showing that miR-221 is significantly upregulated in metastatic CRC cell lines and tissues. miR-221 overexpression enhances, whereas miR-221 depletion reduces CRC cell migration and invasion in vitro and metastasis in vivo. We identify RECK as a direct target of miR-221, reveal its expression to be inversely correlated with miR-221 in CRC samples and show that its re-introduction reverses miR-221-induced CRC invasiveness. Collectively, miR-221 is an oncogenic miRNA which may regulate CRC migration and invasion through targeting RECK.     

miR-125b-1-3p inhibits trophoblast cell invasion by targeting sphingosine-1-phosphate receptor 1 in preeclampsia

Preeclampsia (PE) is the leading cause of maternal and perinatal mortality and morbidity. Understanding the molecular mechanisms underlying placentation facilitates the development of better intervention of this disease. MicroRNAs are strongly implicated in the pathogenesis of this syndrome. In current study, we found that miR-125b-1-3p was elevated in placentas derived from preeclampsia patients. Transfection of miR-125b-1-3p mimics significantly inhibited the invasiveness of human trophoblast cells, whereas miR-125b-1-3p inhibitor enhanced trophoblast cell invasion. Luciferase assays identified that S1PR1 was a novel direct target of miR-125b-1-3p in the placenta. Overexpression of S1PR1 could reverse the inhibitory effect of miR-125b-1-3p on the invasion of trophoblast cells. These findings suggested that abnormal expression of miR-125b-1-3p might contribute to the pathogenesis of preeclampsia.     

p75 neurotrophin receptor inhibits invasion and metastasis of gastric cancer

The p75 neurotrophin receptor (p75NTR) is a focus for study at present. However, its function in gastric cancer was not elucidated. Here, we investigated its relation with metastasis of gastric cancer. By immunohistochemistry, we found that the positive rate of p75NTR expression in metastatic gastric cancer was 15.09% (16 of 106), which was lower compared with nonmetastatic gastric cancer (64.15%; 68 of 106). The average staining score in nonmetastatic gastric cancer was significantly higher than in metastatic gastric cancer (1.21 +/- 0.35 versus 0.23 +/- 0.18; P<0.01). p75NTR protein level was also lowly expressed in the highly liver-metastatic gastric cancer cell line XGC9811-L compared with other gastric cancer cell lines by Western blotting. It could also significantly inhibit the in vitro adhesive, invasive, and migratory and in vivo metastatic abilities of gastric cancer cell lines SGC7901 and MKN45 by reducing urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9 proteins and by increasing tissue inhibitor of matrix metalloproteinase (TIMP)-1 protein. Further studies showed that p75NTR could suppress the nuclear factor-kappaB (NF-kappaB) signal. SN50, a specific inhibitor of NF-kappaB, which could inhibit in vitro invasive and migratory abilities of gastric cancer cells, reduced expression of uPA and MMP9 proteins and increased expression of TIMP1 protein. Taken together, p75NTR had the function of inhibiting the invasive and metastatic abilities of gastric cancer cells, which was mediated, at least partially, by down-regulation of uPA and MMP9 proteins and up-regulation of TIMP1 protein via the NF-kappaB signal transduction pathway. Our studies suggested that p75NTR may be used as a new potential therapeutic target in metastatic gastric cancer.     

MiR-219-5p inhibits hepatocellular carcinoma cell proliferation by targeting glypican-3

MicroRNAs (miRNAs) have been linked to the molecular pathogenesis of many cancers. In this study, we found that miR-219-5p was significantly downregulated in 83 HCC tissues and three HCC cell lines, compared to their non-tumor counterparts. MiR-219-5p expression correlated with tumor size, histological differentiation, and overall survival time in HCC patients. We also found that miR-219-5p could inhibit cell proliferation in vitro and arrest cell cycle at the G1 to S transition. Further studies identified that miR-219-5p reduced both the mRNA and protein levels of glypican-3 (GPC3). These findings indicate that miR-219-5p exerts tumor-suppressive effects in hepatic carcinogenesis through negative regulation of GPC3 expression.     

MicroRNA-5195-3p plays a suppressive role in cell proliferation,migration and invasion by targeting MYO6 in human non-small cell lung cancer

MiRNA-5195-3p (miR-5195-3p), a recently discovered and poorly studied miRNA, has been reported to suppress bladder cancer cell behavior. However, its regulatory role in non-small cell lung cancer (NSCLC) remains unclear. Here, the expression of miR-5195-3p was found to be reduced in NSCLC tissues and cells. The in vitro experiments showed that miR-5195-3p upregulation repressed cell proliferation, migration and invasion by CCK-8 and transwell assays. In addition, MYO6 was predicted and confirmed as a potential target of miR-5195-3p by Bioinformatics analysis, Luciferase reporter assay and western blot analysis. There was significantly negative correlation between miR-5195-3p and MYO6 in NSCLC tissues. Furthermore, MYO6 knockdown exhibited similar effects to those of miR-5195-3p overexpression in NSCLC cells, and restored MYO6 expression reversed the inhibitory effects of miR-5195-3p. Therefore, these results demonstrate that miR-5195-3p functions as a tumor suppressor by directly modulating MYO6 expression in NSCLC cells, and may be an innovative candidate target for NSCLC therapy.