PCAT-1 Expression Research Articles

Biological functions of PCAT-1/ SOX4 in cell proliferation and invasion of breast cancer.

Breast cancer (BC) is one of the most common fatal cancers. Recent studies have identified the vital role of long noncoding RNA (lncRNAs) in the development and progression of BC. In this research, lncRNA PCAT-1 was studied to identify how it functioned in the metastasis of BC. PCAT-1 expression of tissues was detected by real-time quantitative polymerase chain reaction (RT-qPCR) in 50 BC patients. Cell proliferation, wound healing assay and transwell assay were used to observe the biological behavior changes of BC cells through knockdown or overexpression of PCAT-1. In addition, RT-qPCR and Western blot assay were performed to discover the potential target protein of PCAT-1 in BC. PCAT-1 expression level in BC samples was higher than that of adjacent ones. Besides, cell proliferation, migrated ability and cell invaded ability of BC cells were inhibited after PCAT-1 was silenced. Cell proliferation, migration and invasion of BC cells were promoted after PCAT-1 was overexpressed. In addition, SOX4 was downregulated after silence of PCAT-1 in BC cells, while SOX4 was upregulated after overexpression of PCAT-1 in BC cells. Furthermore, SOX4 was upregulated in BC tissues and was positively associated with PCAT-1. Our study uncovers a new oncogene in BC and suggests that PCAT-1 could enhance BC cell proliferation, migration and invasion via targeting SOX4, which provided a novel therapeutic target for BC patients.

PCAT-1' s role in wound healing impairment: Mitochondrial dysfunction and bone marrow stem cell differentiation inhibition via PKM2/β-catenin pathway and its impact on implant osseo-integration.

This study focused on unravelling the role of PCAT-1 in wound-healing process, particularly its impact on regenerative and osteogenic abilities of mesenchymal stem cells (MSCs). We delved into how PCAT-1 regulates mitochondrial oxidative phosphorylation (OXPHOS) and interacts with pivotal molecular pathways, especially β-catenin and PKM2, using human bone marrow-derived MSCs. MSCs were cultured under specific conditions and PCAT-1 expression was modified through transfection. We thoroughly assessed several critical parameters: MSC proliferation, mitochondrial functionality, ATP production and expression of wound healing and osteogenic differentiation markers. Further, we evaluated alkaline phosphatase (ALP) activity and mineral deposition, essential for bone healing. Our findings revealed that overexpressing PCAT-1 significantly reduced MSC proliferation, hampered mitochondrial performance and lowered ATP levels, suggesting the clear inhibitory effect of PCAT-1 on these vital wound-healing processes. Additionally, PCAT-1 overexpression notably decreased ALP activity and calcium accumulation in MSCs, crucial for effective bone regeneration. This overexpression also led to the reduction in osteogenic marker expression, indicating suppression of osteogenic differentiation, essential in wound-healing scenarios. Moreover, our study uncovered a direct interaction between PCAT-1 and the PKM2/β-catenin pathway, where PCAT-1 overexpression intensified PKM2 activity while inhibiting β-catenin, thereby adversely affecting osteogenesis. This research thus highlights PCAT-1's significant role in impairing wound healing, offering insights into the molecular mechanisms that may guide future therapeutic strategies for enhancing wound repair and bone regeneration.

Expression pattern of PCAT1, PCAT2, and PCAT5 lncRNAs and their value as diagnostic biomarkers in patients with gastric cancer

BackgroundGastric cancer (GC), is a complex multifactorial neoplasm with a high mortality and prevalence rate all over the world. Hence, it is necessary to identify the multiple pathways that are previously unknown and are involved in its initiation and progression. Recently, it has become clear that long non-coding RNAs (lncRNAs) play a crucial role in the onset and spread of cancer. The current study assessed the lncRNAs PCAT1, PCAT2, and PCAT5 expression in primary gastric tumors and adjacent noncancerous tissues. Methods90 pairs of GC and adjacent noncancerous tissue samples were obtained. Total RNA was extracted, then cDNA was synthesized. Using quantitative reverse transcriptase PCR (qRT-PCR), PCAT1, PCAT2, and PCAT5 expression levels were evaluated. Using the SPSS statistical package, the correlation between clinicopathological characteristics and the expression of PCAT1, PCAT2, and PCAT5 was investigated. The diagnostic value of PCAT1, PCAT2, and PCAT5 in GC was assessed using the receiver operating characteristic (ROC) curve analysis. ResultsCompared to surrounding non-cancerous tissues, PCAT1, PCAT2, and PCAT5 were all significantly overexpressed in tumoral tissues (P = 0.001, P = 0.019, and P = 0.0001, respectively). PCAT5 expression was significantly associated with gender (P = 0.020), according to our research. The ROC curve's findings indicated that PCAT1, PCAT2, and PCAT5 may each function as poor diagnostic biomarkers, with respective AUC values of 64 %, 60 %, and 68 %, specificity values of 68 %, 60 %, and 76 %, and sensitivity values of 55 %, 72 %, and 52 %. ConclusionOur research suggested that PCAT1, PCAT2, and PCAT5 may be engaged in promoting and developing GC cells as a novel oncogene because of the increased expression of PCAT1, PCAT2 and PCAT5 in tumor tissues of GC patients. Additionally, PCAT1, PCAT2, and PCAT5 can be thought of as poor diagnostic biomarkers for GC case detection.

Exosomal lncRNA PCAT1 Promotes Tumor Circulating Cell-Mediated Colorectal Cancer Liver Metastasis by Regulating the Activity of the miR-329-3p/Netrin-1-CD146 Complex.

Objective This study explored the colorectal cancer exosome lncRNA prostate cancer associated transcript 1– (PCAT1) mediated circulating tumors and the mechanism of cell colorectal cancer liver metastasis. Methods Exosomes were extracted from the primary colorectal cancer (CRC) cell lines HCT116 and SW480 and cultured with T84 and human umbilical vein endothelial (HUVE) cells. The expression of PCAT1 and miR-329-3p was detected by real-time quantitative polymerase chain reaction (RT-qPCR), the expression of Netrin-1, CD146, and epithelial mesenchymal transition (EMT) related proteins was detected by Western blot, the proliferation activity of T84 cells was detected by cell counting kit 8 (CCK-8), and cell migration was detected by Transwell. The expression of the F-actin signal was detected by immunofluorescence after coculture of exosomes with human umbilical vein endothelial cells (HUVECs). Changes in subcutaneous tumor and liver nodule size after PCAT1 deletion were observed in a mouse model of liver metastasis from rectal cancer. Results PCAT1 expression was upregulated in primary cell lines and their exosomes. After exosomes were cocultured with colorectal cancer tumor circulating T84 cells, the expression of Netrin-1 and CD146 was upregulated, the expression of miR-329-3p was downregulated, the proliferation and migration ability of T84 cells were enhanced, and EMT occurred. After knocking down PCAT1, the above phenomenon was reversed. Similarly, after exosomes were cocultured with HUVECs, the expression of the F-actin signal increased, and after PCAT1 was knocked down, the F-actin signal also decreased. PCAT1 regulates miR-329-3p/Netrin-1 and affects the biological behavior of T84 and F-actin signal expression in HUVECs. In a mouse model of colorectal cancer liver metastasis, knocking down PCAT1 significantly reduced the nodules formed by liver metastasis in mice. Conclusions LncRNA PCAT1 derived from colorectal cancer exosomes regulates the activity of the Netrin-1-CD146 complex in circulating tumor cells (CTCs) to promote the occurrence of colorectal cancer EMT and liver metastasis and provides new molecular targets for the treatment of colorectal cancer liver metastasis.

Relationship between long non-coding RNA PCAT-1 expression and gefitinib resistance in non-small-cell lung cancer cells

BackgroundGefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been used as first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, during treatment, cancer cells often develop resistance to gefitinib, the mechanisms of which are not fully understood. This study was designed to elucidate the expression and role of long non-coding RNA (lncRNA)-PCAT-1, a potential biomarker for drug resistance and a therapeutic target for NSCLC, in gefitinib resistance in NSCLC cells.MethodsIn this study, we verified differential PCAT-1 expression in NSCLC gefitinib-resistant tissues or cells. PCAT-1 knockdown, clone formation, Transwell, flow cytometry, and immunofluorescence assays were used to verify the correlation between PCAT-1 and gefitinib sensitivity. A nude mouse tumor-bearing model verified that PCAT-1 can reverse gefitinib resistance in vivo. Then, a PI3K/Akt agonist was used to verify the possible mechanism of PCAT-1 action.ResultsPCAT-1 is highly expressed in gefitinib-resistant NSCLC tissues and cells. PCAT-1 knockdown enhanced gefitinib sensitivity and gefitinib-induced apoptosis in H1299/GR cells. PCAT-1 knockdown reduced tumor volume and weight, and reversed acquired gefitinib resistance in vivo. PCAT-1 knockdown inhibited AKT and GSK3 phosphorylation in H1299/GR cells. A PI3K/AKT agonist reversed PCAT-1 knockdown-mediated enhancement of gefitinib sensitivity in H1299/GR cellsConclusionPCAT-1 knockdown improves sensitivity to gefitinib by inhibition of AKT and GSK3 phosphorylation in NSCLC. PCAT-1 is as potential target for improving the clinical efficacy of gefitinib.

LncRNA PCAT1 enhances cell proliferation, migration and invasion by miR-508-3p/NFIB axis in diffuse large B-cell lymphoma.

In previous studies, PCAT1 has been proved to be a key carcinogenic driver in hepatocellular carcinoma. However, the regulatory mechanism of PCAT1 remains poorly understood in diffuse large B-cell lymphoma (DLBCL). The expression of PCAT1, miR-508-3p and NFIB in DLBCL was detected by RT-qPCR assay. CCK-8 assay and transwell assay were used to measure cell proliferation, migration and invasion of DLBCL cells. Western blot assay was used to explore the protein expression of NFIB. Dual-Luciferase reporter assay was applied to measure the correlation between PCAT1, miR-508-3p and NFIB. PCAT1 was demonstrated to be upregulated in DLBCL tissues and cell lines. Besides, PCAT1 expression was associated with clinical stage and IPI score of DLBCL patients. Moreover, overexpression of PCAT1 promoted DLBCL cell proliferation, migration and invasion in vitro. Mechanistic investigation displayed that PCAT1 interplayed with miR-508-3p, while NFIB was a target gene of miR-508-3p. Further, miR-508-3p was in a downtrend while NFIB was increased in DLBCL tissues and cell lines. MiR-508-3p overexpression repressed DLBCL cell growth and metastasis, while PCAT1 overexpression reversed the inhibitory effect of miR-508-3p on the progression of DLBCL. Moreover, NFIB silencing suppressed DLBCL cell proliferation, migration and invasion, whereas PCAT1 vector or miR-508-3p knockdown destroyed the inhibitory of si-NFIB on the progression of DLBCL. Taken together, our findings validated that PCAT1 acted as completive endogenous RNA by sponging miR-508-3p and upregulating NFIB to facilitate DLBCL cell proliferation, migration and invasion.

Knockdown of lncRNA PCAT1 Enhances Radiosensitivity of Cervical Cancer by Regulating miR-128/GOLM1 Axis.

PurposeCervical cancer (CC) is the fourth most common cancer with high death rate in females. The study aims to detect the mechanism of long non-coding RNA (LncRNA) PCAT1 on radiosensitivity of CC.MethodsThe expression of PCAT1, miR-128 and GOLM1 in CC tissues and cells was measured by qRT-PCR. Different doses of X-ray were used for radiation treatment of CC cells and 6 Gy was chosen to perform the following experiments. The proliferation, migration and invasion of CC cells were measured by MTT assay, wound healing assay and transwell assay, respectively. The target relationships among PCAT1, miR-128 and GOLM1 were predicted by StarBase and TargetScan and verified by luciferase reporter assay. The protein level of GOLM1 was determined by Western blot. The xenograft tumor model was constructed in nude mice to verify the effect of PCAT1 on radiosensitivity of CC in vivo.ResultsThe PCAT1 expression was upregulated in CC tissues and cells. PCAT1 silencing enhances radiosensitivity of CC cells on proliferation, migration and invasion. MiR-128 was the target of PCAT1 and was negatively regulated by PCAT1. Upregulation of miR-128 enhances radiosensitivity of CC cells on proliferation, migration and invasion. GOLM1 was a target of miR-128 and was negatively regulated by miR-128. Upregulation of GOLM1 and downregulation of miR-128 both reversed the enhanced effect of PCAT1 knockdown on radiosensitivity of CC cells, which partly promoted the proliferation, migration and invasion of CC cells.ConclusionSilencing of PCAT1 enhanced radiosensitivity of CC via targeting miR-128/GOLM1, which provided a new idea for treating CC.

Tumor-derived urinary exosomal long non-coding RNAs as diagnostic biomarkers for bladder cancer.

Bladder cancer (BC) is the sixth most common malignancy in men and 17th in women. Exosomal long non-coding RNAs (lncRNAs) have been defined as a novel biomarker for BC. The aim of this study is to evaluate the clinical significance of urine exosomal PVT-1, ANRIL and PCAT-1 as a biomarker in BC patients with tumors classified as T1 or T2. Exosomes were isolated from urine of BC patients and healthy donors, then characterized according to their shape, size, and exosome markers by Electron Microscopy, Dynamic light scattering, and Western blotting. Exosomal lncRNAs extraction was done to determine the expression levels of PVT-1, ANRIL and PCAT-1 by qRT-PCR. ANRIL and PCAT-1 expression was significantly higher in BC patients compared to normal subjects. To evaluate the performance of the identified lncRNAs for BC detection, we performed ROC curves analysis. The diagnostic accuracy of ANRIL and PCAT-1, measured by AUC, was 0.7229 (sensitivity = 46.67 % and specificity = 87.5 %) and 0.7292 (sensitivity = 43.33 % and specificity = 87.5 %). Transcript levels of lncRNAs in urinary exosomes are potential diagnostic biomarkers in bladder cancer.

Long non-coding RNA PCAT-1 promotes cardiac fibroblast proliferation via upregulating TGF-β1.

Recently, the vital functions of long non-coding RNAs (lncRNAs) in many diseases have been explored. This study aims to identify the function of lncRNA PCAT-1 in the development of atrial fibrillation (AF). Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to detect PCAT-1 expression in right atrial appendage (RAA) tissues of 51 AF patients and 35 patients with sinus rhythm (SR). Besides, cell proliferation assay was conducted in AC16 cells with PCAT-1 knockdown. Molecular mechanism of PCAT-1 in influencing the progression of AF was finally investigated. PCAT-1 expression was higher in RAA tissues of AF patients than those of SR patients. Moreover, knockdown of PCAT-1 inhibited proliferation in AC16 cells. Transforming growth factor-β1 (TGF-β1) was a target of PCAT-1 and its expression in AF tissues positively correlated to PCAT-1 expression. PCAT-1 could promote cell proliferation of AF via promoting TGF-β1, which may provide a new theory for AF development.

PCAT1 promotes the proliferative and migratory potentials of ovarian cancer via targeting NEK2.

The aim of this study was to clarify the potential role of PCAT1 in the occurrence and development of ovarian cancer (OC). Expression levels of PCAT1 and NEK2 in OC tissues and cell lines were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Correlation between PCAT1 expression with tumor stage and prognosis of OC patients was analyzed. Knockdown or over-expression of PCAT1 and NEK2 were achieved by siRNA or lentivirus transfection, respectively. Subsequently, cell viability, apoptosis, cell cycle progression and migration were determined by cell counting kit-8 (CCK-8), flow cytometry and transwell assay, respectively. Furthermore, the protein levels of relative genes in Wnt pathway were detected by Western blot. PCAT1 was highly expressed in OC tissues and cell lines, especially in tumor tissues with stage III-IV compared with stage I-II. The prognosis of OC patients with higher expression of PCAT1 was significantly worse than those with lower expression. In vitro experiments confirmed that PCAT1 knockdown obviously inhibited proliferative and migratory potentials, whereas induced apoptosis of OC cells. No significant changes were observed in cell cycle progression of OC cells after knockdown or overexpression of PCAT1. Meanwhile, overexpression of PCAT1 remarkably upregulated the expression level of NEK2, which was the target gene of PCAT1. Interestingly, NEK2 knockdown could obviously suppress cell migration. Furthermore, Western blot results elucidated that PCAT1 knockdown could inhibit the protein levels of relative genes in Wnt pathway in OC cells. PCAT1 was highly expressed in OC tissues than adjacent normal tissues. PCAT1 overexpression significantly promoted proliferative and migratory potentials, whereas inhibited apoptosis of OC cells through upregulating NEK2 expression via Wnt pathway.

Long noncoding RNA PCAT-1 accelerates the metastasis of pancreatic cancer by repressing RBM5.

The role of long noncoding RNAs (lncRNAs) is vital in tumor progression. Our study aims to identify the role of PCAT-1 in the metastasis of pancreatic cancer. Real time-quantitative polymerase chain reaction (RT-qPCR) was used to measure PCAT-1 expression in 50 pancreatic cancer patients' tissues. Furthermore, to identify the function of PCAT-1 in pancreatic cancer in vitro wound healing assay and transwell assay were conducted. Besides, RT-qPCR and Western blot assay were performed to explore the underlying mechanism. The expression level of PCAT-1 was significantly upregulated in pancreatic cancer samples compared with adjacent tissues. Moreover, cell migration and cell invasion were inhibited via knockdown of PCAT-1 in pancreatic cancer cells. Moreover, the mRNA and protein expression of RBM5 was upregulated via knockdown of PCAT-1 in pancreatic cancer cells. Furthermore, the RBM5 expression level was negatively related to the PCAT-1 expression level in pancreatic cancer tissues. This study suggests that PCAT-1 acts as an oncogene in pancreatic cancer and promotes cell metastasis via inhibiting RBM5, which might be a novel therapeutic strategy in pancreatic cancer.

Long noncoding RNA PCAT-1 promoted ovarian cancer cell proliferation and invasion by suppressing KLF6.

Recently, the role of long noncoding RNAs (lncRNAs) in tumor progression has caught attention in numerous researchers. In our investigation, lncRNA PCAT-1 was studied to identify how it functioned in the progression of ovarian cancer. LncRNA PCAT-1 expression was detected by quantitative Real-time polymerase chain reaction (qRT-PCR) in both ovarian cancer cells and tissue samples. Furthermore, to identify the function of PCAT-1 in ovarian cancer, cell proliferation, transwell assay and Matrigel assay were conducted. In addition, by performing qRT-PCR and Western blot assay, the underlying mechanism was explored. PCAT-1 expression was remarkably higher in ovarian cancer samples when compared with that in corresponding ones. Moreover, cell proliferation, migration and invasion were inhibited after PCAT-1 was knocked down in ovarian cancer cells. Moreover, the mRNA and protein expression of KLF6 (Krüppel-like factor 6) was upregulated after PCAT-1 was knocked down. Furthermore, the KLF6 expression level was negatively related to the PCAT-1 expression level in ovarian cancer samples. We showed that PCAT-1 promotes the progression of ovarian cancer through enhancing cell metastasis and proliferation via suppressing KLF6, which might be a novel therapeutic strategy in ovarian cancer.

Profound Decrease in Glomerular Arginine Transport by CAT (Cationic Amino Acid Transporter)-1 Contributes to the FLT-1 (FMS-Like Tyrosine Kinase 1) Induced Preeclampsia in the Pregnant Mice.

Endothelial dysfunction because of nitric oxide inactivation has been suggested to play a role in the pathogenesis of preeclampsia. During pregnancy, L-arginine transport by CAT-1 (cationic amino acid transporter 1), the only transporter for eNOS (endothelial nitric oxide synthase) is inhibited. We hypothesize that maternal arginine deficiency contributes to the development of preeclampsia. Adenovirus-mediated overexpression of sFlt-1 (soluble fms-like tyrosine kinase 1) in virgin and pregnant mice resulted in glomerular endotheliosis, hypertension, and albuminuria. L-arginine prevented the increase in blood pressure and albuminuria in Flt-1 pregnant but not in Flt-1 virgin mice. Flt-1 augmented arginine transport in pregnant but not in virgin dames. Ex vivo inhibition of CAT-2 leaving exclusively CAT-1 activity, decreased arginine transport velocities in Flt-1 animals more prominently in pregnant dames. Phosphorylated CAT-1/CAT-1 increased in pregnant, sFlt-1-pregnant, and sFlt-1 virgin mice. CAT-2 increased in Flt-1-pregnant and Flt-1-virgin dames. L-arginine augmented arginine transport in pregnant and Flt-pregnant mice and prevented the increase in pCAT-1 and CAT-2 expression. Glomerular cGMP (cyclic guanosine monophosphate) generation as a measure of eNOS activity was decreased in all Flt-1 treated animals. L-arginine abolished the decrease in cGMP levels only in Flt-1-pregnant mice. In conclusion, glomerular endothelial NO generation is compromised in Flt-1-pregnant mice because of CAT-1 inhibition induced by a combined effect of pregnancy and preeclampsia which involves: phosphorylation of CAT-1 and induction of CAT-2. These processes contribute to the clinical syndrome of preeclampsia in mice and are prevented by L-arginine.

LncRNA PCAT-1 regulates the proliferation, metastasis and invasion of cervical cancer cells.

To investigate the effects of long non-coding RNA (lncRNA) PCAT-1 on the proliferation, metastasis, and invasion of cervical cancer cells. LncRNA PCAT-1 small interfering RNA (siRNA) and negative siRNA were transfected into cervical cancer cell lines and the expression of lncRNA PCAT-1 in cells was confirmed by Real-time quantitative polymerase chain reaction (qPCR). Cell counting kit-8 (CCK-8) and colony formation assay were applied to detect the effect of lncRNA PCAT-1 on cell proliferation. The wound-healing assay was applied to test the effect of lncRNA PCAT-1 on cell metastasis. Matrigel cell invasion assay was performed to detect the impact of lncRNA PCAT-1 expression on invasion. After transfected with the long non-coding PCAT-1 siRNA into cervical cancer cell lines for 48 h, the lncRNA PCAT-1 cells were significantly down-regulated. The results of CCK-8, clonogenic and wound-healing assay showed that the decreased expression of lncRNA PCAT-1 attenuated the proliferation and metastasis of cells. The results of matrigel cell invasion assay manifested that the decreased expression of lncRNA PCAT-1 could reduce the invasion ability. The up-regulation of lncRNA PCAT-1 was associated with poor prognosis of patients with cervical cancer. LncRNA PCAT-1 siRNA transfected into cervical cancer cell lines can effectively lower the expression of lncRNA PCAT-1, while lncRNA PCAT-1 expression can inhibit the proliferation, metastasis and invasion abilities of cervical cancer cells.

Long noncoding RNA PCAT-1 acts as an oncogene in osteosarcoma by reducing p21 levels

Long non-coding RNA (lncRNA) is emerging as a critical regulator in multiple cancers. Recently, lncRNA PCAT-1 was found to be up-regulated in prostate cancer and hepatocellular carcinoma, exerting oncogenic effects. However, the biological function and regulatory mechanism of PCAT-1 remain unclear in osteosarcoma (OS). In this study, we reported that PCAT-1 expression was also upregulated in OS tissues, and its overexpression was remarkably associated with tumor size, Enneking stage, tumor node metastasis (TNM) stage and metastasis in patients with OS. Knockdown of PCAT-1 suppressed OS cells proliferation, migration and invasion in vitro, and inhibited the tumorigenicity of OS cells in vivo. Mechanistic investigations revealed that PCAT-1 could interact with EZH2, thereby repressing p21 expression. Additionally, rescue experiments indicated that PCAT-1 functioned as an oncogene partly via suppressing p21 in OS cells. Collectively, our findings demonstrate that PCAT-1 is a new candidate for use in OS diagnosis, prognosis and therapy.

The long noncoding RNA PCAT-1 links the microRNA miR-215 to oncogene CRKL-mediated signaling in hepatocellular carcinoma

The long non-coding RNA (lncRNA) PCAT-1 resides in the chromosome 8q24 cancer-risk locus and acts as a vital oncogene during tumorigenesis and progression. However, how PCAT-1 is post-transcriptionally regulated, for example, by small ncRNAs, such as microRNAs (miRNAs) is largely unknown. Here, we report how miRNAs regulate PCAT-1 expression and also investigate the biological significance of this regulation in hepatocellular carcinoma (HCC). We found that miR-215, a P53-inducible miRNA, is a key regulator of PCAT-1 expression in HCC and identified an interaction between miR-215 and PCAT-1 in dual luciferase reporter gene assays. We also found that post-transcriptional silencing of PCAT-1 by miR-215 or PCAT-1 siRNAs significantly inhibited proliferation of HCC cells and, conversely, that inhibition of endogenous miR-215 up-regulated PCAT-1 expression and promoted cell viability. The tumor-suppressing role of miR-215 was further confirmed in an in vivo mouse HCC xenograft model. Of note, gene profiling assays suggested that the kinase CRK-like proto-oncogene, adaptor protein (CRKL), is a potential downstream target of the miR-215-PCAT-1 axis in HCC, and we demonstrated that CRKL silencing significantly suppresses cell proliferation. Taken together and considering the essential role of CRKL in cancer cells, we propose that the TP53-miR-215-PCAT-1-CRKL axis might represent an important regulatory pathway in HCC. In summary, our results highlight the involvement of several ncRNAs in HCC and thus provide critical insights into the molecular pathways operating in this malignancy.

The association of rs710886 in lncRNA PCAT1 with bladder cancer risk in a Chinese population

ObjectiveThe long noncoding RNA PCAT1 is an important gene involved in urinary tumors. In this study, we aimed to explore the association between polymorphisms in PCAT1 and bladder cancer susceptibility. MethodsA two-stage case-control study was conducted to assess the association between four tagging SNPs (i.e., rs4871771, rs1902432, rs16901904 and rs710886) and bladder cancer risk. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated with unconditional univariate and multivariate logistic regression. ResultsAt the first stage of discovery, we identified that SNP rs710886A>G was significantly associated with bladder cancer risk (OR=0.86, 95% CI=0.74–0.99, P=0.046). At the following stage of validation, individuals with GG genotype were found to have a significant reduction in bladder cancer risk compared with those carrying AA genotype (adjusted OR=0.83, 95% CI=0.74–0.93, P=0.001). Furthermore, stratified analyses showed that protective effect of rs710886 was more pronounced in subgroup of age>60 and never smoking, and had little to do with sex. Besides, rs710886 was identified as an eQTL for PCAT1. G allele was consistent with lower PCAT1 expression. ConclusionThis study indicates that genetic variants in lncRNA PCAT1 were associated with bladder cancer susceptibility and the SNP rs710886 may act as a potential biomarker for bladder cancer risk.

Upregulated lncRNA-PCAT1 is closely related to clinical diagnosis of multiple myeloma as a predictive biomarker in serum.

The purpose of this study was to explore serum PCAT-1 expression in multiple myeloma (MM) and examine the potential usefulness of this molecule as a biomarker for diagnosis in MM. Serum samples were collected from 60 newly diagnosed untreated MM patients, and 48 healthy controls. Serum PCAT-1 expression levels were detected by RT-qPCR. In addition, correlations between the relative expression of serum PCAT-1 and the concentrations of lactic acid dehydrogenase (LDH), β2M, λ light chain and κ light chain were assessed. It was found that the relative expression of serum PCAT-1 in MM patients (81.02 ± 136.9) was higher than that in healthy controls (3.17 ± 5.75) (U= 307.0, P< 0.0001) and was significantly correlated with β2M concentration (r= 0.461, P= 0.0002), but not with LDH, κ light and λ light chain concentration (r= 0.061, P= 0.641; r= 0.007, P= 0.956; r=-0.090, P= 0.499 respectively). Additionally, it was significantly correlated with different isotype of MM (H= 7.464, P= 0.024). The AUC of the ROC curve of serum PCAT-1 was 0.892 (95% CI 0.833-0.950), which was higher than other markers. Combining PCAT-1 and β2M together, the sensitivity was highest compared with other markers alone, or combined. The expression levels of serum PCAT-1 in MM patients were significantly higher than that in healthy controls, suggesting that it may be useful in the auxiliary diagnosis of MM.

PCAT-1, a Long Noncoding RNA, Regulates BRCA2 and Controls Homologous Recombination in Cancer

Impairment of double-stranded DNA break (DSB) repair is essential to many cancers. However, although mutations in DSB repair proteins are common in hereditary cancers, mechanisms of impaired DSB repair in sporadic cancers remain incompletely understood. Here, we describe the first role for a long noncoding RNA (lncRNA) in DSB repair in prostate cancer. We identify PCAT-1, a prostate cancer outlier lncRNA, which regulates cell response to genotoxic stress. PCAT-1 expression produces a functional deficiency in homologous recombination through its repression of the BRCA2 tumor suppressor, which, in turn, imparts a high sensitivity to small-molecule inhibitors of PARP1. These effects reflected a posttranscriptional repression of the BRCA2 3'UTR by PCAT-1. Our observations thus offer a novel mechanism of "BRCAness" in sporadic cancers.

A Tissue-specific Long Noncoding RNA Controls Homologous Recombination in Prostate Cancer

Our group has recently identified 121 novel long non-coding RNAs (lncRNAs) whose dysregulated expression stratifies prostate cancer progression. One of these, PCAT1, was upregulated in aggressive disease, and PCAT1 expression inversely correlated with expression levels of BRCA2, a homologous recombination (HR) repair protein. The purpose of this study was to determine the role of PCAT1 in DNA repair and response to genotoxic stress.