lncRNA CASC11 promotes cancer cell proliferation in bladder cancer through miRNA-150

Long noncoding RNAs (lncRNAs) CASC11 is an oncogenic lncRNA in gastric cancer and colorectal cancer. Our study aimed to investigate the role of lncRNA CASC11 in bladder cancer. In this study we showed that plasma lncRNA CASC11 was upregulated, while plasma miRNA-150 was downregulated in patients with early-stage bladder cancer than in healthy controls. Altered expression of plasma lncRNA CASC11 and miRNA-150 separated patients with bladder cancer from healthy controls. lncRNA CASC11 expression was inversely correlated with miRNA-150 expression in patients with bladder cance but not in healthy controls. Overexpression of lncRNA CASC11 mediated the inhibition of miRNA-150 expression in cancer cells, while miRNA-150 overexpression did not significantly alter lncRNA CASC11 expression. lncRNA CASC11 overexpression promoted, while miRNA-150 overexpression inhibited cancer cell proliferation. miRNA-150 also attenuated the enhancing effects of lncRNA CASC11 overexpression on cancer cell proliferation. However, overexpression of lncRNA CASC11 showed no significant effects on cancer cell migration and invasion. Therefore, lncRNA CASC11 may promote cancer cell proliferation in bladder cancer, and the actions of lncRNA CASC11 are likely through miRNA-150.     

The lncRNA HNF1A‐AS1 is a negative prognostic factor and promotes tumorigenesis in osteosarcoma

Recent studies have revealed that long noncoding RNA HNF1A‐antisense 1 (HNF1A‐AS1) plays an important role in the development of several human malignancy entities. However, the expression and function of HNF1A‐AS1 in the carcinogenesis and development of osteosarcoma remains unknown. In this study, we detected the HNF1A‐AS1 levels in human osteosarcoma tissues and cell lines by quantitative real‐time polymerase chain reaction (qRT‐PCR), and investigated its role in osteosarcoma by using in vitro assays. Our study showed that HNF1A‐AS1 expression was significantly up‐regulated in human osteosarcoma tissues and cell lines compared with their normal counterparts, and its expression level was positively correlated with the distance metastasis (P = 0.009) and tumour stage (P = 0.019). Moreover, Kaplan–Meier curves with the log‐rank test showed that higher expression of HNF1A‐AS1 conferred a significantly poorer survival and multivariate Cox proportional hazards analysis revealed that HNF1A‐AS1 was an independent risk factor of overall survival. In addition, the expression of HNF1A‐AS1 in serum is correlated with patients’ status and receiver operating characteristic (ROC) curve analysis demonstrated that HNF1A‐AS1 could distinguish patients with osteosarcoma from healthy individuals (the area under curve 0.849, P < 0.001). Furthermore, in vitro knockdown of HNF1A‐AS1 by siRNA significantly inhibited cell proliferation and G₁/S transition, and suppressed migration and invasion by reducing the epithelial‐mesenchymal transition (EMT) program in osteosarcoma cells. Taken together, our data suggested that HNF1A‐AS1 is a novel molecule involved in osteosarcoma progression, which may provide as a potential diagnostic, prognostic biomarker and therapeutic target.     

The lncRNA TP73‐AS1 promotes ovarian cancer cell proliferation and metastasis via modulation of MMP2 and MMP9

Ovarian cancer is one of the most common gynecologic malignancy with poor prognosis. Recently, long noncoding RNAs (lncRNAs) have been identified as key regulators in cancer development. The current study investigated the role of lncRNA P73 antisense RNA 1T (TP73‐AS1) in ovarian cancer. Quantitative real‐time polymerase chain reaction determined the expression levels of TP‐73AS1, matrix metallopeptidases (MMPs) messenger RNA. Cell proliferative ability, cell invasion, and migration were CCK‐8 and colony formation, and transwell invasion and migration assays, respectively. The protein levels of matrix metallopeptidase 2 (MMP2) and MMP9 were measured by Western blot. TP73‐AS1 was upregulated in the ovarian cancer tissues and ovarian cancer cells, and upregulation of TP73‐AS1 was associated with poor prognosis. Knockdown of TP73‐AS1 significantly suppressed cell proliferation, invasion, and migration of SKOV3 cells, and overexpression of TP73‐AS1 promoted cell proliferation, invasion, and migration of OVCA429 cells. In addition, knockdown of TP73‐AS1 suppressed the in vivo tumor growth. Tumor metastasis RT² profiler polymerase chain reaction array showed that MMP2 and MMP9 was significantly upregulated by TP73‐AS1 overexpression in ovarian cancer cells. TP73‐AS1 overexpression enhanced the expression of MMP2 and MMP9 in ovarian cancer cells. Knockdown of MMP2 and MMP9 attenuated the effects of TP73‐AS1 overexpression on cell invasion and migration. The clinical data showed that MMP2 and MMP9 were upregulated and positively correlated with TP73‐AS1 expression in ovarian cancer tissues. Collectively, our results demonstrated the oncogenic role of TP73‐AS1 in ovarian cancer, and targeting TP73‐AS1 may represent a novel approach in battling against ovarian cancer.     

Effect of the autism-associated lncRNA Shank2-AS on architecture and growth of neurons

The pathogenic mechanism of autism is complex, and current research has shown that long noncoding RNAs (lncRNAs) may play important roles in this process. The antisense lncRNA of SH3 and multiple ankyrin repeat domains 2 (Shank2-AS) is upregulated in patients with autism spectrum disorder (ASD), whereas the expression of its sense strand gene Shank2 is downregulated. In neuronal cells, Shank2-AS and Shank2 can form a double-stranded RNA and inhibit Shank2 expression. Overexpression of Shank2-AS decreases neurite numbers and lengths, thereby inhibiting the proliferation of neuronal cells and promoting their apoptosis. Overexpression of Shank2 inhibits the abovementioned effects of Shank2-AS, and transfection of a vector containing the 10th intron of Shank2 (Shank2-AS is reverse-transcribed from this region) also blocks the function of Shank2-AS. Shank2 small interfering RNA plays a role similar to Shank2-AS. Therefore, Shank2-AS is abnormally expressed in patients with ASD and may affect the structure and growth of neurons by regulating Shank2 expression, thereby facilitating the development of ASD.     

Retracted: Long noncoding RNA HAGLROS regulates apoptosis and autophagy in colorectal cancer cells via sponging miR-100 to target ATG5 expression

The aim of this study was to explore the relationship between the expression of HOXD antisense growth-associated long noncoding RNA (HAGLROS) and prognosis of patients with colorectal cancer (CRC), as well as the roles and regulatory mechanism of HAGLROS in CRC development. The HAGLROS expression in CRC tissues and cells was detected. The correlation between HAGLROS expression and survival time of CRC patients was investigated. Moreover, HAGLROS was overexpressed and suppressed in HCT-116 cells, followed by detection of cell viability, apoptosis, and the expression of apoptosis-related proteins and autophagy markers. Furthermore, the association between HAGLROS and miR-100 and the potential targets of miR-100 were investigated. Besides, the regulatory relationship between HAGLROS and PI3K/AKT/mTOR pathway was elucidated. The results showed that HAGLROS was highly expressed in CRC tissues and cells. Highly expression of HAGLROS correlated with a shorter survival time of CRC patients. Moreover, knockdown of HAGLROS in HCT-116 cells induced apoptosis by increasing the expression of Bax/Bcl-2 ratio, cleaved-caspase-3, and cleaved-caspase-9, and inhibited autophagy by decreasing the expression of LC3II/LC3I and Beclin-1 and increasing P62 expression. Furthermore, HAGLROS negatively regulated the expression of miR-100, and HAGLROS controlled HCT-116 cell apoptosis and autophagy through negatively regulation of miR-100. Autophagy related 5 (ATG5) was verified as a functional target of miR-100 and miR-100 regulated HCT-116 cell apoptosis and autophagy through targeting ATG5. Besides, HAGLROS overexpression activated phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. In conclusion, a highly expression of HAGLROS correlated with shorter survival time of CRC patients. Downregulation of HAGLROS may induce apoptosis and inhibit autophagy in CRC cells by regulation of miR-100/ATG5 axis and PI3K/AKT/mTOR pathway.     

LncRNA RP6-65G23.1 accelerates proliferation and inhibits apoptosis via p-ERK1/2/p-AKT signaling pathway on keratinocytes

Long non-coding RNAs (LncRNAs) play essential roles in the development of various diseases including hepatic carcinoma, melanoma, and psoriasis. Meanwhile, lncRNA-RP6-65G23.1 was upregulated in psoriasis. However, it is still unclear whether lncRNA-RP6-65G23.1 expression is upregulated and contributes to keratinocytes proliferation and apoptosis, and which mechanisms are responsible for these processes. The aims of this study are to address these issues. RP6-65G23.1 was significantly upregulated in M5-stimulated keratinocytes and stimulated the proliferation and inhibited the apoptosis of HaCaT cells. Knockdown of RP6-65G23.1 resulted in defects of growth and increased rates of apoptosis in HaCaT cells, while overexpression of RP6-65G23.1 manifested the opposite effects. Consistently, the expression of antiapoptotic proteins Bcl-xl and Bcl2 were decreased in RP6-65G23.1-knockdown cells but elevated in RP6-65G23.1 overexpression cells. In addition, RP6-65G23.1 depletion blunted the activity of extracellular regulated kinase 1/2 (ERK1/2) and AKT signaling pathways and induced G₁/S-growth arrest. By contrast, overexpression of RP6-65G23.1 activates the ERK1/2 and AKT signaling pathways and inhibits the expression of p21 and p27 in an AKT-dependent manner leading to promote the G1/S progression. Our results suggested that lncRNA-RP6-65G23.1 would contribute to the pathogenesis of psoriasis by regulating the proliferation and apoptosis of keratinocytes via the p-ERK1/2 and p-AKT pathways.     

The contradictory effects of nitric oxide in caerulein-induced acute pancreatitis in rats

This study was planned to observe the effects of nitric oxide synthesis on the antioxidative defense enzymes and pancreatic tissue histology in caerulein-induced acute pancreatitis. Acute pancreatitis was induced by intraperitoneal injections of 50 µg/kg caerulein, L-arginine used for NO induction and N^ω-nitro-L-arginine methyl ester (L-NAME) used for NO inhibition. In the caerulein group acinar cell degeneration, interstitial inflammation, oedema and haemorrhage were detected. Pancreatic damage scores were decreased with both NO induction and inhibition (p<0.05). MDA, GSH-Px, CAT, GSH and SOD activities were significantly changed in the caerulein group and indicated increased oxidative stress. Both NO induction and inhibition decreased this oxidative stress. It is concluded that both nitric oxide induction and inhibition ameliorated caerulein-induced acute pancreatitis. The findings indicate that a certain amount of NO production has beneficial effects in experimental acute pancreatitis, but uncontrolled over-production of NO may be detrimental.     

RNA-Seq analysis and functional characterization revealed lncRNA NONRATT007560.2 regulated cardiomyocytes oxidative stress and apoptosis induced by high glucose

Hyperglycemia in diabetic patients would cause cardiomyocytes oxidative stress and apoptosis due to the excessive reactive oxygen species (ROS) accumulation, leading to progressive deterioration of cardiac structure and function. Long noncoding RNAs (lncRNAs) play essential roles on controlling oxidative stress and apoptotic activity. In the present study, RNA sequencing was used to detect the differentially expressed lncRNAs during high glucose-induced cardiomyocytes oxidative stress and apoptosis. A total of 306/400 lncRNAs were identified as differentially expressed, including 156/198 lncRNAs with increased expression and 150/202 lncRNAs with decreased expression at 24 hours/48 hours after high-glucose stimulation respectively. Among these dysregulated lncRNAs, 45 lncRNAs were consistently differentially expressed in cardiomyocytes at both two time points after high-glucose stimulation. Twenty lncRNAs were upregulated and 25 lncRNAs were downregulated at both 24 hours and 48 hours, respectively. The top three upregulated lncRNAs, NONRATT029805.2, NONRATT007560.2, and NONRATT002486.2 were selected for functional studies to determine the role in oxidative stress-related apoptosis. The results showed that inhibition of non-ratt007560.2 could abate the formation of ROS and reduce apoptosis, suggesting NONRATT007560.2 might play critical roles in the development of cardiomyopathy. The dysregulated lncRNAs might participate in regulating cardiomyocytes oxidative stress and apoptosis. These findings would be important theoretical and experimental basis for investigation on diabetic cardiomyopathy pathogenesis     

lncRNA作为竞争性内源RNA在非小细胞肺癌中的作用

长链非编码RNA(long non-coding RNA,lncRNA)参与肿瘤的多种生理、病理进程.研究表明,lncRNA可通过与微小RNA (microRNA, mi RNA)反应元件相互作用,并与其他RNA分子形成竞争性内源RNA (competing endogenous RNA,ceRNA)的调控网络,参与基因的表达调控.lncRNA以ceRNA方式参与非小细胞肺癌(non-small cell lung cancer,NSCLC)的发生发展过程,为揭示NSCLC的分子机理开拓了新的思路,也为NSCLC的治疗提供新的靶点.本文在课题组前期发现NSCLC相关ceRNA基础上,主要讨论lncRNA作为ceRNA在NSCLC中高表达、低表达及治疗相关方面的作用.     

Effect of microRNA-27a-5p on apoptosis and inflammatory response of pancreatic acinar cells in acute pancreatitis by targeting PTEN

To investigate the apoptosis and inflammatory response of microRNA-27a-5p (miR-27a-5p) in pancreatic acinar cells of acute pancreatitis (AP) and its related mechanisms. Rat pancreatic acinar cell line AR42J was treated with caerulein (10nmol/L) to construct an acute pancreatitis cell model. Quantitative real-time polymerase chain reaction was performed to measure the expression of miR-27a-5p; The miR-27a-5p mimic was transfected into cell, and the apoptosis rate of the cells was detected by flow cytometry; The levels of TNF-α, IL-1, and IL-6 in the culture supernatant were determined by enzyme-linked immunosorbent assay; TargetScans database predicted and dual luciferase reporter gene assay verified the relationship between miR-27a-5p and the phosphatase and tensin homolog deleted on chromosome 10 (PTEN); The recovery experiment explored the apoptosis and the effects of inflammatory responses. The expression of miR-27a-5p decreased gradually (P < 0.05) and the expression of PTEN increased gradually (P < 0.05) with the prolongation of acting time. Upregulation of miR-27a-5p significantly promoted cell apoptosis (P < 0.05) and inhibited inflammatory response (P < 0.05); The TargetScans database predicted that the 3'UTR of PTEN contains a base complementary to the miR-27a-5p seed region. Cotransfection of wild-type vector (PTEN-WT) with miR-27a-5p mimic or miR-27a-5p inhibitor significantly affected the relative activity of luciferase (P < 0.05), and no significant impact was observed in mutant PTEN-MUT. Compared with miR-27a-5p + pcDNA group, transfection of miR-27a-5p mimic and pcDNA-PTEN significantly increased the expression of PTEN (P < 0.05), decreased the apoptotic rate (P < 0.05), and increased the inflammatory response (P < 0.05). miR-27a-5p induced apoptosis and inhibited the inflammatory response of pancreatic acinar cells in AP by targeting PTEN.     

LncRNA Linc00511 promotes osteosarcoma cell proliferation and migration through sponging miR-765

Long noncoding RNA (lncRNA) Linc00511 is a novel lncRNA, and it was reported to play important roles in the progression and carcinogenesis of several tumors. However, the expression and biological roles of Linc00511 in osteosarcoma were still unknown. In this research, we showed that the expression of Linc00511 was upregulated in osteosarcoma samples and cell lines. Ectopic expression of Linc00511 promoted osteosarcoma cell growth, colony formation, and migration. Moreover, overexpression of Linc00511 enhanced the epithelial-mesenchymal transition progression in osteosarcoma cell. In addition, we showed that elevated expression of Linc00511 suppressed microRNA-765 (miR-765) expression and promoted apurinic/apyrimidinic endonuclease 1 (APE1) expression in osteosarcoma cell. The expression of miR-765 was downregulated in osteosarcoma cells and samples and was negatively related to Linc00511 expression in osteosarcoma tissues. Ectopic expression of miR-765 inhibited osteosarcoma cell growth and migration. Furthermore, we showed that Linc00511 overexpression promoted MG-63 cells proliferation, colony formation, and migration via downregulation of miR-765. These results suggested that Linc00511 played as an oncogene in the development of osteosarcoma.     

Knockdown of long noncoding RNA urothelial carcinoma associated 1 inhibits colorectal cancer cell proliferation and promotes apoptosis via modulating autophagy

Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been implicated in the growth and metastasis of colorectal cancer (CRC), and autophagy contributes to tumorigenesis and cancer cell survival. However, the regulatory role of UCA1 in CRC cell viability by modulating autophagy remains unclear. In the present study, a significant positive correlation was observed between UCA1 and microtubule-associated protein 1 light chain 3 (LC3) levels, and the elevated UCA1 was negatively correlated with the PKB/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in 293T cells. Downregulation of UCA1 inhibited autophagy activation and cell proliferation, whereas the apoptosis was increased and the cell cycle was arrested in G2 stage. The next results showed that UCA1 was markedly upregulated in Caco-2 cells. Knockdown of UCA1 significantly decreased the LC3-II and autophagy-related gene 5 (ATG5) protein levels and resulted in an increase in p62 expression. Conversely, the autophagy activator rapamycin (RAPA) reversed the effects. Furthermore, downregulated UCA1 decreased Caco-2 cells population in the G1 phase and increased the cells number in G2 phage. The cell proliferation was inhibited, and apoptosis rate was promoted. More important, RAPA could also abrogate the changes induced by knockdown of UCA1. Collectively, these data demonstrated that downregulated UCA1 induced autophagy inhibition, resulting in suppressing cell proliferation and promoting apoptosis, which suggested that UCA1 might serve as a potential new oncogene to regulate CRC cells viability by modulating autophagy.     

SBF2-AS1: An oncogenic lncRNA in small-cell lung cancer

The long noncoding RNAs (lncRNAs) SBF2 antisense RNA 1 (SBF2-AS1) was found to act as an oncogenic lncRNA in non–small-cell lung cancer (NSCLC), but the role of SBF2-AS1 in small-cell lung cancer (SCLC) was still unclear. The purpose of this study was to provide the clinical significance and biological function of SBF2-AS1 in SCLC. In our results, SBF2-AS1 was found to be upregulated in SCLC tissues compared with NSCLC tissues or adjacent normal lung tissues. Besides, SBF2-AS1 expression was also elevated in SCLC cell lines compared with the normal bronchial epithelial cell line or NSCLC lines. Moreover, high expression of SBF2-AS1 was associated with clinical stage, tumor size, lymph node metastasis and distant metastasis in SCLC patients. Survival analysis showed SCLC patients with high expression of SBF2-AS1 had shorter overall survival than patients with low expression of SBF2-AS1, and high expression of SBF2-AS1 acted as an independent poor prognostic factor for overall survival in SCLC patients. The study in vitro suggested inhibition of SBF2-AS1 obviously depressed cell proliferation, migration, and invasion in SCLC. In conclusion, SBF2-AS1 acts as a novel oncogenic lncRNA in SCLC.     

Overexpression of ZEB2‐AS1 promotes epithelial‐to‐mesenchymal transition and metastasis by stabilizing ZEB2 mRNA in head neck squamous cell carcinoma

The long noncoding RNAs (lncRNAs) have been increasingly appreciated as key players underlying tumourigenesis and hold great potentials as prognostic biomarkers and therapeutic targets. However, their roles in head neck squamous cell carcinoma (HNSCC) have remained incompletely known. Here, we sought to reveal the oncogenic roles and clinical significance of a tumour‐associated lncRNA, zinc finger E‐box binding homeobox 2 antisense RNA 1 (ZEB2‐AS1), in HNSCC. ZEB2‐AS1 was aberrantly overexpressed in a fraction of HNSCC samples. Its overexpression significantly associated with large tumour size, cervical node metastasis and reduced overall and disease‐free survival. Antisense oligonucleotides (ASO)‐mediated ZEB2‐AS1 depletion markedly inhibited cell proliferation, migration and invasion while triggered apoptosis in HNSCC cells in part via modulating ZEB2 mRNA stability. Enforced overexpression of ZEB2 largely attenuated the phenotypic changes resulted from ZEB2‐AS1 inhibition except the impaired cell proliferation. In addition, ZEB2‐AS1 was required for TGF‐β1‐induced epithelial‐mesenchymal transition (EMT) in vitro. Significantly reduced tumour growth and lung metastasis were observed in ZEB2‐AS1‐depleted cells in HNSCC xenograft animal models. Taken together, our findings reveal that overexpression of ZEB2‐AS1 associates with tumour aggressiveness and unfavourable prognosis by serving as a putative oncogenic lncRNA and a novel prognostic biomarker in HNSCC.