Noncoding RNA Prostate Cancer-associated Transcript Research Articles

MicroRNA-155 downregulates long noncoding RNA prostate cancer-associated transcript 29 in hepatocellular carcinoma to suppress cancer cell invasion and migration.

Long noncoding RNA (lncRNA) prostate cancer-associated transcript 29 (PCAT29) is known to suppress several cancers, but its participation in hepatocellular carcinoma (HCC) remains elusive. This study tried to explore PCAT29 function in HCC. In this study, a total of 62 HCC patients were enrolled. Tissue samples were collected from all 62 patients to isolate RNA samples. Quantitative reverse transcription polymerase chain reaction was applied for the expression analysis of PCAT29 and microRNA-155 (miR-155) in these tissue samples. The 62 HCC patients were followed up for 5 years to explore the prognostic value of PCAT29 for HCC. Correlations were analyzed using linear regression. IntaRNA 2.0 was used to predict the interaction between PCAT29 and miR-155. The role of PCAT29 and miR-155 in regulating HCC cell invasion and migration was evaluated by Transwell assay. We found that PCAT29 expression was downregulated in HCC and miR-155 expression was upregulated in HCC compared to nontumor samples (p < 0.001). Downregulation of PCAT29 was found to be closely associated with poor survival of HCC patients. MiR-155 was inversely correlated with PCAT29. It was predicted that miR-155 could target PCAT29. In HCC cells, miR-155 overexpression resulted in reduced PCAT29 expression (p < 0.05). MiR-155 counteracted the inhibitory effects of PCAT29 overexpression on HCC cell migration and invasion. These results suggest that PCAT29 may be a potential prognostic biomarker and a novel therapeutic target for treating HCC.

Long non-coding RNA prostate cancer-associated transcript 6 inhibited gefitinib sensitivity of non-small cell lung cancer by serving as a competing endogenous RNA of miR-326 to up-regulate interferon-alpha receptor 2

ABSTRACT The critical roles of lncRNAs in drug resistance of malignancies have been widely recognized. This investigation aims to study the function of lncRNA PCAT6 in the resistance of non-small cell lung cancer (NSCLC) to gefitinib. In our study, we demonstrated that prostate cancer-associated transcript 6 (PCAT6) was upregulated in gefitinib-resistant NSCLC. PCAT6 knockdown inhibited gefitinib resistance of NSCLC, as indicated by decreased IC50 value, proliferation, and metastasis, and increased cell apoptosis. Besides, PCAT6 could directly target miR-326 in gefitinib-resistant NSCLC cells and augment NSCLC resistance to gefitinib by serving as ceRNA of miR-326. Furthermore, interferon-alpha receptor 2 (IFNAR2) was validated as a downstream target of miR-326 and miR-326 reduced resistance to gefitinib by inhibiting IFNAR2 expression. Our investigation identified that PCAT6 enhanced gefitinib resistance of NSCLC via miR-326/IFNAR2 axis, which might offer a new therapeutic strategy against gefitinib resistance of NSCLC patients.

LncRNA PCAT6 facilitates cell proliferation and invasion via regulating the miR-326/hnRNPA2B1 axis in liver cancer.

Liver cancer is one of the most common malignant human tumors with the highest morbidity and mortality rates of all cancer types in China. Evidence suggests that long non-coding RNA prostate cancer-associated transcript 6 (PCAT6) plays an essential role in tumor progression. However, the roles and mechanism of PCAT6 in liver cancer remain unclear. The present study showed that the expression of PCAT6 and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) was upregulated in liver cancer tissues compared with non-cancerous tissues and were associated with poor overall survival time, whereas microRNA (miR)-326 expression was downregulated. Moreover, knockdown of PCAT6 significantly inhibited the proliferation and invasion of liver cancer cells in vitro and in vivo. A dual-luciferase reporter gene assay demonstrated that PCAT6 could bind to miR-326 and that hnRNPA2B1 was a direct target gene of miR-326. Mechanistically, silenced PCAT6 suppressed the malignant phenotype of liver cancer cells through upregulating the inhibitory effect of miR-326 on hnRNPA2B1 expression. Taken together, these data demonstrated that knockdown of PCAT6 inhibited liver cancer progression through regulation of the miR-326/hnRNPA2B1 axis, suggesting that PCAT6 functions as an oncogene and may be a useful biomarker for the future diagnosis and treatment of liver cancer.

Knockdown of long non-coding RNA prostate cancer-associated transcript 1 inhibits the proliferation and metastasis of tongue squamous cell carcinoma cells by upregulating p21.

Long non-coding RNA (lncRNA) prostate cancer-associated transcript 1 (PCAT-1) is a long non-coding RNA involved in the development of various cancer types. Tongue squamous cell carcinoma (TSCC) is the most frequently diagnosed type of oral cancer worldwide. The present study aimed to explore the role of lncRNA PCAT-1 in TSCC, and to provide a preliminary assessment of the downstream pathways involved. The expression levels of lncRNA PCAT-1 in TSCC specimens were first assessed. Subsequently, lncRNA PCAT-1 was knocked down in TSCC cell lines and the resulting effect on the proliferation and apoptosis, as well as the metastatic and invasive potential of TSCC cells was investigated. To assess the downstream signaling resulting from lncRNA PCAT-1 inhibition, the expression of p21 was also detected. The results indicated that lncRNA PCAT-1 was upregulated in clinical TSCC compared with peri-tumor tissues. Inhibition of lncRNA PCAT-1 resulted in reduced proliferation and apoptosis of TSCC cells, in addition to the suppression of migration and invasion. Furthermore, the expression of p21 was induced following lncRNA PCAT-1 inhibition. Collectively, the present study demonstrated an oncogenic role for lncRNA PCAT-1 in TSCC; inhibition of lncRNA PCAT-1 reduced the growth, metastasis and invasion of TSCC, at least in part via the induction of p21 signaling.

Silencing of long non-coding RNA PCAT6 restrains gastric cancer cell proliferation and epithelial-mesenchymal transition by targeting microRNA-15a.

Gastric cancer (GC) is a high mortality disease. We studied the function and mechanism of long non-coding RNA prostate cancer-associated transcript 6 (lncRNA PCAT6) on cell proliferation and epithelial-mesenchymal transition (EMT) in GC cells. CCK-8, flow cytometry and colony formation assay were respectively used to detect the cell viability, apoptosis and colony formation. PCAT6 and miR-15a expression were changed by cell transfection. Moreover, the level of Cyclin D1, p53, Bax, Cleaved caspase-3 and relate-proteins of EMT and cell pathways were investigated by Western blot. Besides, the level of miR-15a and PCAT6 was tested by RT-qPCR. Besides, the target relation between miR-15a and PCAT6 were tested by luciferase assay. PCAT6 was highly expressed in GC cells and tissues. Silencing of PCAT6 restrained the relate-proteins of cell proliferation and EMT. Furthermore, PCAT6 reversely regulated miR-15a and miR-15a inhibitor reversed the efficacy of sh-PCAT6 in cell proliferation and EMT. PCAT6 restrained the relate-proteins of RB/E2F and Wnt/β-catenin pathways and miR-15a reverse this progress. Finally, PCAT6 was a target of miR-15a. Silencing of lncRNA PCAT6 restrained proliferation and EMT of GC cells by targeting miR-15a via RB/E2F and Wnt/β-catenin pathways.

PCAT1/miR-129/ABCB1 axis confers chemoresistance in non-small cell lung cancer.

Long noncoding RNA prostate cancer-associated transcript 1 (PCAT1) is oncogenic and causes progression of non-small cell lung cancer (NSCLC). We hypothesized that PCAT1 might be involved in the acquisition of chemoresistance of NSCLC cells to treatment with cisplatin (DDP). Here, we show that PCAT1 and ATP-binding cassette sub-family B member 1 (ABCB1) are highly expressed in NSCLC tissues and cell lines, and regulate the growth and apoptosis of these cells. Compared with those in DDP-sensitive patients, PCAT1 and ABCB1 are highly expressed in the tumors of DDP-resistant patients, and such overexpression correlates with a shorter overall survival of these patients. Knockdown of PCAT1 or upregulation of miR-129 led to apoptosis and sensitized the DDP-resistant cells to DDP. The 3' UTR activity of PCAT1 and ABCB1, which was increased by PCAT1 overexpression, was shown to harbor an miR-129 binding site. DDP resistance is induced by elevated ABCB1 expression, which involves binding of miR-129 in DDP resistant cells. These findings suggest that the PCAT1/miR-129/ABCB1 axis may be a potential target for the treatment of DDP-resistant oat cell cancer.

Long noncoding RNA PCAT-1 knockdown prevents the development of ovarian cancer cells via microRNA-124-3p.

Long noncoding RNA prostate cancer-associated transcript 1 (PCAT-1) is overexpressed in human malignancies and its silence abates the exaggeration of cancers. Whereas, the activity of PCAT-1 silence in ovarian cancer (OC) remains elusive. Here, our study was designed to corroborate the function of PCAT-1 silence in cellular activities and the molecular mechanisms. PCAT-1 in human ovarian tumor tissue specimens and cell lines (A2780 and SKOV3) were quantified by real-time quantitative reverse polymerase chain reaction (qRT-PCR). Reinforced silence of PCAT-1 and microRNA (miR)-124-3p was established by transfection and identified by qRT-PCR. The viability, apoptosis as well as migration and invasion were examined. Western blot was exploited for analysis of proteins involved in proliferation, apoptosis, migration and invasion, and signaling transduction. OC tissues showed the accumulation of PCAT-1. Silencing PCAT-1 caused the impediment of proliferation, migration, and invasion with the increase in apoptosis. PCAT-1 knockdown repressed the expression of cyclin D1, CDK6, p53, Bax, cleaved caspase-3, metallopeptidases, and vimentin with the restoration of miR-124-3p. However, the roles of PCAT-1 silence were weakened in the absence of miR-124-3p. PCAT-1 silence caused decrease in Wnt3a, β-catenin, and phosphorylation of protein kinase B and mechanistic target of rapamycin was abolished by miR-124-3p inhibitor. The tumor-suppressive role of PCAT-1 silence was mediated by miR-124-3p.

Polymorphisms in Long Noncoding RNA-Prostate Cancer-Associated Transcript 1 Are Associated with Lung Cancer Susceptibility in a Northeastern Chinese Population.

Long noncoding RNAs (lncRNAs) are a new class of potential biomarkers and therapeutic targets for cancer. In this study, we chose four single nucleotide polymorphisms (SNPs) in lncRNA-PCAT1 (rs1026411 G>A, rs12543663 A>C, rs710886 T>C, and rs16901904 T>C) to investigate the association between genetic variant in lncRNA-PCAT1 and susceptibility to lung cancer. The study was a hospital-based case–control study including 561 cancer-free controls and 468 lung cancer cases. Genotyping of four SNPs was conducted by using Taqman® allelic discrimination methods. All statistical analyses were performed by using IBM SPSS Statistics 22 software. We failed to find significant associations between four SNPs and lung cancer risk in all models. However, polymorphisms in rs1026411 and rs710886 were observed to have significant associations with susceptibility to non-small cell lung cancer (AG vs. GG: odds ratio [OR]a = 0.701, p* = 0.020 and AA+AG vs. GG: ORa = 0.711 [superscript “a” refers to OR adjusted by age, gender, and smoking], p* = 0.017 [asterisks “*” refers to p adjusted by age, gender, and smoking] for rs1026411; CT vs. TT: ORa = 0.723, p* = 0.047 and CC+CT vs. TT: ORa = 0.729, p* = 0.038 for rs710886). Besides, the rs1026411 polymorphism had a similar association with lung adenocarcinoma risk (AG vs. GG: ORa = 0.663, p* = 0.019 and AA+AG vs. GG: ORa = 0.685, p* = 0.020). Polymorphisms in rs710886 and rs16901904 were observed to be associated with lung squamous cell carcinoma risk (CC+CT vs. TT: ORa = 0.638, p* = 0.040 for rs710886; CC vs. TT: ORa = 2.582, p* = 0.033 and CC vs. TT+CT: ORa = 2.381, p* = 0.048 for rs16901904). In addition, there were no significant results in gene–environmental interactions in both additive and multiplicative models. Our results suggested that polymorphisms in lncRNA-PCAT1 might be associated with lung cancer susceptibility in a northeastern Chinese population. The results of gene–environmental interactions were not significant in lung cancer.

Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene TMPRSS2 and lncRNA PRCAT38 in Prostate Cancer.

Prostate cancer is a common carcinoma in males, the development of which involves the androgen receptor (AR) as a key regulator. AR transactivation induces the high expression of androgen-regulated genes, including transmembrane protease serine 2 (TMPRSS2) and long noncoding RNA prostate cancer-associated transcript 38 (PRCAT38). PRCAT38 and TMPRSS2 are both located on chromosome 21, separated by a series of enhancers. PRCAT38 is a prostate-specific long noncoding RNA that is highly expressed in cancer tissue as compared to normal tissue. Here, we show chromatin looping by enhancers E1 and E2 with the promoters for PRCAT38 and TMPRSS2, indicating the co-regulation of PRCAT38 and TMPRSS2 by the same enhancers. The knockout of enhancer E1 or E2 simultaneously impaired the transcription of PRCAT38 and TMPRSS2 and inhibited cell growth and migration. Moreover, the loop formation and enhancer activity were mediated by AR/FOXA1 binding and the activity of acetyltransferase p300. Our findings demonstrate the utilization of shared enhancers in the joint regulation of two oncogenes in prostate cancer cells.

The Role of Long Non-coding RNA Prostate Cancer-Associated Transcript 1 in Prostate Cancer.

This study aimed to investigate the role of prostate cancer associated transcript 1 (PCAT1) underlying the molecular mechanisms of prostate cancer. Using GSE29886 data set downloaded from Gene Expression Omnibus database, we screened the differentially expressed genes (DEGs) in PCAT1-siRNA interfering (PCAT1-siRNA) LNCaP cells compared with control-siRNA cells. Transcription factor (TF) and tumor-associated genes database were used to obtain oncogenes and tumor suppressor genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to investigate the function and pathways of DEGs. Subnetwork was further analyzed using BioNet. A total of 93 DEGs were identified. KEGG analysis showed downregulated TF genes (ID1 and ID3) were enriched in transforming growth factor-β pathway, whereas upregulated genes were involved in pathways associated with immune system, environmental sensing, and metabolism. GO analysis showed that downregulated genes were primarily enriched in cell cycle-related biological functions and upregulated DEGs were related to immune response, exogenous genetic material response, and viral response. Centromere protein F (CENPF) was identified as the central node of the regulatory subnetwork. In the PCAT1 knockdown LNCaP cells, the CENPF, ID1, and ID3 were obviously decreased based on the RT-PCR (quantitative real-time reverse transcription PCR) analysis. PCAT1 may be involved in cell cycle and proliferation of prostate cancers by mediating the expression of CENPF, ID1, and ID3.

Long Non-Coding RNA Prostate Cancer-Associated Transcript 7 (PCAT7) Induces Poor Prognosis and Promotes Tumorigenesis by Inhibiting mir-134-5p in Non-Small-Cell Lung (NSCLC).

BackgroundLong non-coding RNA PCAT7 has been revealed to participate in tumorigenesis of various cancers. However, the mechanism of PCAT7 in non-small cell lung cancer (NSCLC) has not been identified. Hence, this study aimed to determine the function of PCAT7 in NSCLC.Material/MethodsThe expression level of PCAT7 in 96 pairs of NSCLC tissues and 6 cell lines was detected by qRT-PCR. Proliferation assay, flow cytometric analysis, transwell/migration assay, and Western blotting assay were performed to detect the relation between PCAT7 and malignant behaviors of NSCLC cells in vitro, including cell proliferation, apoptosis, migration, invasion, and epithelial-to-mesenchymal transition (EMT). Rescue assays were carried out to confirm the contribution of PCAT7 to the progression of NSCLC cells by targeting miR-134-5p.ResultsPCAT7 was found to be overexpressed in NSCLC tissues (compared with corresponding non-tumor tissues) and NSCLC cells (compared with normal cell line 16-HBE). Overexpression of PCAT7 resulted in the promotion of tumor cell proliferation, inhibition of cells apoptosis, facilitation of cells metastasis, and formation of EMT phenotype, while PCAT7 expression deletion remarkably prohibited cell proliferation, accelerated their apoptosis, weakened metastasis, and reversed EMT to MET. miR-134-5P, as a target gene of PCAT7, restored the effects of down-regulation of PCAT7.ConclusionsThese findings demonstrate that PCAT7 participates in tumor progression in NSCLC by inhibiting miR-134-5p.

Diagnostic significance of circulating long noncoding RNA PCAT6 in patients with non-small cell lung cancer.

AimWe have previously shown that the long noncoding RNA prostate cancer-associated transcript 6 (PCAT6) promoted the proliferation and invasion of lung adenocarcinoma (LUAD) cells. In this study, the diagnostic significance of tissue and serum PCAT6 was evaluated in non-small cell lung cancer (NSCLC).Materials and methodsTissue expression of PCAT6 was systematically evaluated in five Gene Expression Omnibus datasets (GSE19804, GSE18842, GSE30219, GSE19188, and GSE27262). Circulating and tissue expressions of PCAT6 were detected by quantitative reverse-transcriptase polymerase chain reaction in NSCLC patients from Union Hospital.ResultsPCAT6 was significantly increased in lung cancer tissues and could be used to distinguish LUAD from adjacent normal tissues with an area under the receiver operating characteristic curve (AUC) of 0.9210 (p<0.0001; sensitivity, 98.82%; specificity, 78.57%) in GSE30219, 0.9333 (p<0.0001; sensitivity, 86.67%; specificity, 90.77%) in GSE19188, 0.9584 (p<0.0001; sensitivity, 92.00%; specificity, 96.00%) in GSE27262, and 0.9574 (p<0.0001; sensitivity, 95.89%; specificity, 87.67%) in patients from Union Hospital. As for lung squamous cell carcinoma (LUSC), the AUC of PCAT6 was 0.9567 (p<0.0001; sensitivity, 100%; specificity, 85.71%) in GSE30219, 0.9795 (p<0.0001; sensitivity, 96.30%; specificity, 92.31%) in GSE19188, and 0.9942 (p<0.0001; sensitivity, 100%; specificity, 98.04%) in patients from Union Hospital. We further noticed that the plasma levels of PCAT6 were significantly increased in 73 LUAD and 51 LUSC patients compared with 39 healthy controls (p<0.0001). The AUC of circulating PCAT6 was 0.9213 (p<0.0001; sensitivity, 87.67%; specificity, 97.44%) in LUAD and 0.9583 (p<0.0001; sensitivity, 94.12%; specificity, 100%) in LUSC.ConclusionTogether with our previous findings, our results suggest that PCAT6 could be used as a potential diagnostic and prognostic biomarker in NSCLC.