Search

Background: This work aims to analyze the alterations in the levels of PCA3, PCAT1, PRNCR1, and GAS5 long non-coding RNAs (lncRNAs) after the activation of pDNA-buforin II in PC3 cancer cells. Materials and methods: The synthetic nucleic acid sequence of buforin II was included in the pcDNA3.1(+) Mammalian Expression Plasmid. The accuracy of cloning was assessed by using PCR and enzyme digestion techniques. The vectors were transfected into cells utilizing LipofectamineTM2000. The PC3 cancer cells were evaluated using flow cytometry and wound healing analysis. The expression levels of lncRNAs and apoptotic genes were assessed utilizing real-time PCR, with a significance threshold of P

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14–16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood. [ABSTRACT FROM AUTHOR]

Backgrounds: Given the global prevalence of colorectal cancer (CRC), advancements in prompt and accurate diagnosis are crucial. Long non-coding RNAs (lncRNAs) in serum exosomes are emerging as potential diagnostic biomarkers. This study evaluated the feasibility of using serum exosomal lncRNAs for early-stage CRC diagnosis in clinical practice. Methods: Candidate serum exosomal lncRNAs were identified through an integrated analysis of two GEO datasets (GSE100206 and GSE100063) containing non-coding RNA expression profiles in serum exosomes. Exosomes isolated from participants' serum were validated using transmission electron microscopy (TEM) and immunoblotting. The expression levels of serum exosomal PCAT1 were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis. Results: Serum exosomal PCAT1 levels were evaluated in 150 CRC patients, 66 patients with benign colorectal lesions, and 128 healthy controls. ROC analysis demonstrated high diagnostic efficacy of serum exosomal PCAT1 for CRC. Notably, the predictive performance was sufficient to distinguish early-stage CRC patients. Additionally, the diagnostic value was significant for CRC patients with low serum carcinoembryonic antigen (CEA) levels. Measuring serum exosomal PCAT1 could complement CEA assessment, enhancing CRC diagnostic accuracy. Conclusions: Serum exosomal PCAT1 can complement CEA assessment, aiding in early CRC diagnosis and helping to differentiate the disease, especially in patients with low CEA levels.

Background: The expression of long non‐coding RNA (lncRNA) prostate cancer‐associated ncRNA transcripts 1 (PCAT1) is increased in non‐small cell lung cancer (NSCLC). It stimulates tumour growth and metastasis, but its role in the radioimmune responses remain unknown. We aimed to explore the impacts of PCAT1 on tumorigenesis and radioimmune responses and the underlying molecular mechanisms in NSCLC. Methods: Comprehensive bioinformatics analysis was performed to identify immunosuppressive lncRNAs involved with tumour invasion in NSCLC. The expression levels of PCAT1 were analysed by in situ hybridisation in 55 paired NSCLC tissues and adjacent normal tissues. Both loss‐ and gain‐of‐function assays were performed to examine the effects of PCAT1 and SOX2 on NSCLC cell behaviours in vivo and in vitro. Bioinformatic analyses, chromatin isolation by RNA purification (ChIRP) and dual‐luciferase reporter assays were applied to validate the regulatory effects of PCAT1 on SOX2 expression. Chromatin immunoprecipitation, luciferase and rescue assays were utilised to identify the relationship between SOX2 and the cGAS/stimulator of interferon genes (STING) signalling. Results: PCAT1 was immunosuppressive and related with NSCLC invasion. Increased PCAT1 was negatively correlated with immune cell infiltration in NSCLC. PCAT1 knockdown restrained proliferation, increased apoptosis, and repressed cell metastasis in vivo and in vitro. PCAT1 activated SOX2 that accelerated tumorigenesis and immunosuppression. SOX2 promoted tumour growth through inhibiting cytotoxic T‐cell immunity. Moreover, SOX2 restrained cGAS transcription and hampered downstream type I interferon (IFN)‐induced immune responses. Inhibition of PCAT1/SOX2 in collaboration with radiation further inhibited tumour growth, and initiated the cGAS/STING signalling pathway, which enhanced the immune responses of radiotherapy in NSCLC. Conclusions: PCAT1/SOX2 axis promoted tumorigenesis and immunosuppression through inhibition of cGAS/STING signalling‐mediated T‐cell activation. Inhibition of PCAT1 and SOX2 synergised with radiotherapy to activate the immune response and could serve as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Recent evidence has shown that the induction of ferroptosis is a new therapeutic strategy for advanced prostate cancer (PCa) when used as a monotherapy or in combination with second-generation antiandrogens. However, whether ferroptosis inducers are effective against docetaxel-resistant PCa remains unclear. In addition, the biological role and intrinsic regulatory mechanisms of long noncoding RNAs (lncRNAs) in ferroptosis and chemoresistance are not well understood. In this study, we established two acquired docetaxel-resistant PCa cell lines and found that docetaxel-resistant PCa cells developed tolerance toward ferroptosis. In addition, dysregulated lncRNAs in drug-resistant and -sensitive PCa cells were identified by RNA sequencing, and we identified that prostate cancer-associated transcript 1 (PCAT1) was highly expressed in the docetaxel-resistant PCa cell lines and clinical samples. Overexpression of PCAT1 inhibited ferroptosis and increased docetaxel resistance, which could be attenuated by PCAT1 knockdown. Furthermore, we revealed that PCAT1 inhibited ferroptosis by activating solute carrier family 7-member 11 (SLC7A11) expression via reducing iron accumulation and subsequent oxidative damage. Mechanistically, we demonstrated that PCAT1 interacted with c-Myc and increased its protein stability using nucleotides 1093-1367 of PCAT1 and 151-202 amino acids of c-Myc protein, thereby transcriptionally promoting SLC7A11 expression. In addition, PCAT1 facilitated SLC7A11 expression by competing for microRNA-25-3p. Finally, transcription factor AP-2 gamma (TFAP2C) activated PCAT1 expression at the transcriptional level to reduce ferroptosis susceptibility and enhance chemoresistance. Collectively, our findings demonstrated that TFAP2C-induced PCAT1 promotes chemoresistance by blocking ferroptotic cell death through c-Myc/miR-25-3p/SLC7A11 signaling. [ABSTRACT FROM AUTHOR]

Abstract Background The expression of long non‐coding RNA (lncRNA) prostate cancer‐associated ncRNA transcripts 1 (PCAT1) is increased in non‐small cell lung cancer (NSCLC). It stimulates tumour growth and metastasis, but its role in the radioimmune responses remain unknown. We aimed to explore the impacts of PCAT1 on tumorigenesis and radioimmune responses and the underlying molecular mechanisms in NSCLC. Methods Comprehensive bioinformatics analysis was performed to identify immunosuppressive lncRNAs involved with tumour invasion in NSCLC. The expression levels of PCAT1 were analysed by in situ hybridisation in 55 paired NSCLC tissues and adjacent normal tissues. Both loss‐ and gain‐of‐function assays were performed to examine the effects of PCAT1 and SOX2 on NSCLC cell behaviours in vivo and in vitro. Bioinformatic analyses, chromatin isolation by RNA purification (ChIRP) and dual‐luciferase reporter assays were applied to validate the regulatory effects of PCAT1 on SOX2 expression. Chromatin immunoprecipitation, luciferase and rescue assays were utilised to identify the relationship between SOX2 and the cGAS/stimulator of interferon genes (STING) signalling. Results PCAT1 was immunosuppressive and related with NSCLC invasion. Increased PCAT1 was negatively correlated with immune cell infiltration in NSCLC. PCAT1 knockdown restrained proliferation, increased apoptosis, and repressed cell metastasis in vivo and in vitro. PCAT1 activated SOX2 that accelerated tumorigenesis and immunosuppression. SOX2 promoted tumour growth through inhibiting cytotoxic T‐cell immunity. Moreover, SOX2 restrained cGAS transcription and hampered downstream type I interferon (IFN)‐induced immune responses. Inhibition of PCAT1/SOX2 in collaboration with radiation further inhibited tumour growth, and initiated the cGAS/STING signalling pathway, which enhanced the immune responses of radiotherapy in NSCLC. Conclusions PCAT1/SOX2 axis promoted tumorigenesis and immunosuppression through inhibition of cGAS/STING signalling‐mediated T‐cell activation. Inhibition of PCAT1 and SOX2 synergised with radiotherapy to activate the immune response and could serve as potential therapeutic targets.

Recent evidence has shown that the induction of ferroptosis is a new therapeutic strategy for advanced prostate cancer (PCa) when used as a monotherapy or in combination with second-generation antiandrogens. However, whether ferroptosis inducers are effective against docetaxel-resistant PCa remains unclear. In addition, the biological role and intrinsic regulatory mechanisms of long noncoding RNAs (lncRNAs) in ferroptosis and chemoresistance are not well understood. In this study, we established two acquired docetaxel-resistant PCa cell lines and found that docetaxel-resistant PCa cells developed tolerance toward ferroptosis. In addition, dysregulated lncRNAs in drug-resistant and -sensitive PCa cells were identified by RNA sequencing, and we identified that prostate cancer-associated transcript 1 (PCAT1) was highly expressed in the docetaxel-resistant PCa cell lines and clinical samples. Overexpression of PCAT1 inhibited ferroptosis and increased docetaxel resistance, which could be attenuated by PCAT1 knockdown. Furthermore, we revealed that PCAT1 inhibited ferroptosis by activating solute carrier family 7-member 11 (SLC7A11) expression via reducing iron accumulation and subsequent oxidative damage. Mechanistically, we demonstrated that PCAT1 interacted with c-Myc and increased its protein stability using nucleotides 1093-1367 of PCAT1 and 151-202 amino acids of c-Myc protein, thereby transcriptionally promoting SLC7A11 expression. In addition, PCAT1 facilitated SLC7A11 expression by competing for microRNA-25-3p. Finally, transcription factor AP-2 gamma (TFAP2C) activated PCAT1 expression at the transcriptional level to reduce ferroptosis susceptibility and enhance chemoresistance. Collectively, our findings demonstrated that TFAP2C-induced PCAT1 promotes chemoresistance by blocking ferroptotic cell death through c-Myc/miR-25-3p/SLC7A11 signaling.

Backgrounds: Given the global prevalence of colorectal cancer (CRC), advancements in prompt and accurate diagnosis are crucial. Long non-coding RNAs (lncRNAs) in serum exosomes are emerging as potential diagnostic biomarkers. This study evaluated the feasibility of using serum exosomal lncRNAs for early-stage CRC diagnosis in clinical practice., Methods: Candidate serum exosomal lncRNAs were identified through an integrated analysis of two GEO datasets (GSE100206 and GSE100063) containing non-coding RNA expression profiles in serum exosomes. Exosomes isolated from participants' serum were validated using transmission electron microscopy (TEM) and immunoblotting. The expression levels of serum exosomal PCAT1 were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis., Results: Serum exosomal PCAT1 levels were evaluated in 150 CRC patients, 66 patients with benign colorectal lesions, and 128 healthy controls. ROC analysis demonstrated high diagnostic efficacy of serum exosomal PCAT1 for CRC. Notably, the predictive performance was sufficient to distinguish early-stage CRC patients. Additionally, the diagnostic value was significant for CRC patients with low serum carcinoembryonic antigen (CEA) levels. Measuring serum exosomal PCAT1 could complement CEA assessment, enhancing CRC diagnostic accuracy., Conclusions: Serum exosomal PCAT1 can complement CEA assessment, aiding in early CRC diagnosis and helping to differentiate the disease, especially in patients with low CEA levels., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

OBJECTIVE: 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). PATIENTS AND METHODS: 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. RESULTS: PCAT1 was demonstrated to be up regulated 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. CONCLUSIONS: 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. [ABSTRACT FROM AUTHOR]

Objectives: To build a stronger Pichia pastoris PCAT1 promoter and to identify putative transcriptional factor binding sites (TFBSs) on PCAT1 that affect the activity of the promoter. Result: A synthetic library of PCAT1 was generated by deleting or duplicating putative TFBS motifs in the promoter sequence. CSRE, MIG1, RAP1 and HAP2/3/4 were found to have important effects on PCAT1 activity. The PCAT1 variant P4 with a putative binding site of RAP1 on the promoter sequence showed a stronger activity compared with that of the wild-type PCAT1 and PAOX1, which is the strongest natural P. pastoris promoter that has been reported. This inference was confirmed with EGFP (enhanced green fluorescent protein) and Candida Antarctica lipase B as the reporters. Conclusion: The role of the transcriptional regulator RAP1 may be important in PCAT1 methanol induction. A stronger PCAT1 variant can be constructed by the duplication of the putative binding site of RAP1 on the PCAT1 promoter sequence. This PCAT1 variant has potential value for heterologous protein production, metabolic engineering, and synthetic biology. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are emerging as important modulators of cancer progression, among which prostate cancer-associated transcript 1 (PCAT1) has been shown to be an oncogene in several tumors. However, the clinical significance and biological function of PCAT1 in endometrial carcinoma (EC) remain unclear. In this study, we used 89 EC tissues and HEC-1B, Ishikawa, RL95-2 and AN3CA EC cell lines. We found elevated expression levels of PCAT1 in EC tissues and cell lines using reverse transcription qPCR (RT-qPCR). The prognostic value of PCAT1 was determined using Kaplan–Meier survival and Cox regression analysis. The results showed that higher PCAT1 expression was positively correlated with FIGO stage, myometrial invasion, lymph node metastasis, and a shorter overall survival. A series of functional assays showed that the knockdown of PCAT1 by small interfering RNA (siRNA) targeting PCAT1 (siPCAT1) suppressed cell proliferation, migration and invasion, but promoted apoptosis. Western blot analysis further showed that B-cell lymphoma 2 (Bcl-2), vimentin and N-cadherin were downregulated, but E-cadherin and Bcl-2-associated death promoter (Bad) were upregulated in PCAT1-silenced EC cells. Taken together, our results underscore the oncogenic role of PCAT1 in EC and show that PCAT1 may be a potential therapeutic target in EC treatment.

OBJECTIVE: The aim of this study was to clarify the potential role of PCAT1 in the occurrence and development of ovarian cancer (OC). PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the function of glioma stem cells (GSCs) and the role of PCAT1. This study dissociated the differences between GSCs and glioma cells in terms of apoptosis rate and γH2AX positive cells levels after radiation. Microarray was carried out to detect that expressed PCAT1, and it was testified by RT-qPCR. After transfection, GSCs were used to investigate the influence of PCAT1 on radiation sensitivity. Sphere-formation capability was first examined. Cell apoptosis rate after radiation of 0 Gy or 6 Gy was analyzed by flow cytometry, and the level of γH2AX positive cells after 6 Gy radiation were compared. CCK8 assay was used to investigate the cell proliferation and RT-qPCR was used to examine miR-129-5p and HMGB1 expression. GSCs exhibited great capability in sphere formation and lower expression in apoptosis and γH2AX positive cells rates after 6 Gy radiation. PCAT1 had higher expression in GSCs. PCAT1 knockdown restrained the sphere-formation ability, increased the apoptosis rate and DNA damage under the treatment of radiation. Moreover, knockdown of PCAT1 inhibited the cell proliferation. In addition, silencing PCAT1 could increase the expression of miR-129-5p and decrease the expression of HMGB1. PCAT1 was overexpressed in GSCs and played a facilitating role in radiation resistance. [ABSTRACT FROM AUTHOR]

Background: The prostate cancer-associated non-coding RNA transcript 1 (PCAT-1) is a newly identified long non- coding RNA whose participation in tumorigenesis of a variety of cancers has been observed. In the present study, we aimed at analysis of its expression in breast cancer patients. Subjects and Methods: The expression of PCAT-1 was assessed using real-time reverse transcription polymerase chain reaction in tumor samples obtained from 47newly diagnosed breast cancer patients as well as their corresponding adjacent non-cancerous tissues (ANCTs). Results: We detected significant over-expression of PCAT-1 in 12/47 (25.5%) of tumoral tissues compared with their corresponding ANCTs. However, no significant association has been found between the levels of PCAT-1 transcripts and patients’ clinical data such as tumor size, stage, grade, estrogen and progesterone receptors or Her2/neu status. Conclusion: PCAT-1 is possibly involved in the pathogenesis of fraction of breast cancers. Future studies are needed to evaluate its precise function in breast cancer.

Introduction: Osteosarcoma is a malignant primary bone cancer and is lethal to children and adolescents. Recently, the dysregulation of long noncoding RNAs (lncRNAs) has been shown in various types of cancers. Aim: The present study aimed to examine the role of the lncRNA prostate cancer-associated transcript 1 (PCAT1) in osteosarcoma progression. Materials and methods: The expression levels of relevant genes in clinical samples and cell lines were determined by quantitative real-time polymerase chain reaction. Cell proliferation, invasion and migration were examined by CCK-8 assay, transwell invasion and migration assay, respectively. Cell apoptosis and cell cycle were detected by flow cytometry. Protein levels were detected by Western blot. Results: Our results showed that PCAT1 was upregulated in osteosarcoma tissues when compared to normal bone tissues. PCAT1 was also upregulated in osteosarcoma cell lines when compared to normal bone cell line. The upregulation of PCAT1 was significantly associated with advanced clinical stage, tumor metastasis and shorter overall survival in patients with osteosarcoma. In vitro studies showed that overexpression of PCAT1 in MG-63 cells enhanced cell proliferation, cell invasion and migration and epithelial-to-mesenchymal transition (EMT); decreased cell apoptotic rate; and also caused an increase in cell population at S phase with a decrease in cell population at G0/G1 phase. Knockdown of PCAT1 in U2OS cells suppressed cell proliferation, cell invasion and migration, and EMT; increased cell apoptotic rate; and caused an increase in the cell population at G0/G1 phase with a decrease in cell population at S phase. Conclusion: Taken together, our results suggest the oncogenic role of PCAT1 in osteosarcoma progression. [ABSTRACT FROM AUTHOR]

Extrahepatic cholangiocarcinoma (ECC) is a deadly disease that often responds poorly to conventional chemotherapy or radiotherapy. Long noncoding RNAs (lncRNAs) play important roles in human cancers, including ECC, and recent studies indicated that the lncRNA prostate cancer-associated transcript 1 (non-protein coding) (PCAT1) is involved in multiple cancers. However, the role of PCAT1 in ECC is unclear. Previously, we showed that PCAT1 is up-regulated in both ECC tissue samples and cell lines. Here, we showed that downregulation of PCAT1 following transfection with silencing RNA reduced ECC cell growth and increased cell apoptosis. Additionally, PCAT1 suppression inhibited ECC cell migration and invasion as determined by transwell assay. Furthermore, we determined that PCAT1 is a competing endogenous for microRNA (miR)-122, with bioinformatics analysis and luciferase-reporter assay results demonstrating that PCAT1 regulated WNT1 expression via miR-122. Moreover, PCAT1 downregulation increased levels of glycogen synthase kinase 3β and significantly decreased β-catenin levels in whole cell lysates and nuclear fractions, indicating that PCAT1 silencing inhibited the Wnt/β-catenin-signaling pathway. We also observed that exogenous expression of WNT1 reversed PCAT1-silencing-induced inhibition of ECC cell growth inhibition. These results indicated that PCAT1 silencing inhibited ECC progression by reducing Wnt/β-catenin signaling through miR-122 repression and WNT1 expression. Our findings revealed an important role of PCAT1 in ECC and suggested that PCAT1 might be a potential ECC-related therapeutic target. [ABSTRACT FROM AUTHOR]

Objective The 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. Methods A 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. Results At 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. Conclusion This 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. [ABSTRACT FROM AUTHOR]

Background: The prostate cancer-associated non-coding RNA transcript 1 (PCAT-1) is a newly identified long non- coding RNA whose participation in tumorigenesis of a variety of cancers has been observed. In the present study, we aimed at analysis of its expression in breast cancer patients. Materials and Methods: The expression of PCAT-1 was assessed using real-time reverse transcription polymerase chain reaction in tumor samples obtained from 47newly diagnosed breast cancer patients as well as their corresponding adjacent non-cancerous tissues (ANCTs). Results: We detected significant over-expression of PCAT-1 in 12/47 (25.5%) of tumoral tissues compared with their corresponding ANCTs. However, no significant association has been found between the levels of PCAT-1 transcripts and patients' clinical data such as tumor size, stage, grade, estrogen and progesterone receptors or Her2/neu status. Conclusion: PCAT-1 is possibly involved in the pathogenesis of fraction of breast cancers. Future studies are needed to evaluate its precise function in breast cancer. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most frequently diagnosed cancer in males and its development and progression remains an important area of study. Recently, long non-coding RNAs (lncRNAs) have been evidenced as key players in cancer pathogenesis. Specifically, dysregulation of long non-coding RNA (lncRNA) expression has shown to affect tumor proliferation and metastasis, acting as either tumor suppressors or oncogenes. However, its specific mechanisms and functions in prostate cancer remain unclear. This review provides an overview of currently available information on prostate cancer-related lncRNAs, including GAS5, GAS-007, MEG3, PCA3, PCAT14, PCAT1, PVT1, UCA1, SChLAP1, MALAT1, HOTAIR, and NEAT1 . Notable tumor growth inhibitors include GAS5 and MEG3. GAS5 is evidenced to interfere with the AKT/MTOR signaling pathway through targeting microRNA mir-103. MEG3, however, is proposed to inhibit the cycle, sponge miR-9-5p, and induce gene silencing. PCAT1, PVT1, and UCA1 are important tumor growth promoters. PCAT1 is indicated to be a transcriptional repressor, a mir-145-5P sponge, and a P13K/AKT pathway activator. Studies suggest that PVT1 acts via microRNA targeting and regulating proliferating cell nuclear antigen. UCA1 may sponge miR-204 and miR-331-3p as well as regulate myosin VI. Thorough understanding of these lncRNAs may elucidate new aspects of prostate cancer pathology and serve a pivotal role in developing novel diagnostic and prognostic techniques., Competing Interests: None., (AJCEU Copyright © 2022.)

Long none coding RNAs (lncRNAs) AOC4P , PRNCR1 , and PCAT -1 are dysregulated in various types of malignancies. However, their expression and clinicopathological significances are uncertain in breast cancer (BC). Quantitative real-time polymerase chain reaction (RT- qPCR) was used to measure the expression levels of the selected lncRNAs in tumor tissues obtained from 50 BC patients compared to the normal adjacent tissues (NATs) and 50 clinically healthy normal tissues. Our results revealed a significant downregulation of AOC4P , however, upregulated PRNCR1 and PCAT1 were found in tumor tissues compared to NATs and clinically healthy normal tissues (P < 0.05). Interestingly, remarkable decreased expression of AOC4P was observed in NATs than clinically healthy normal tissues. Dysregulation of the lncRNAs was correlated with worse outcomes of patients. Furthermore, our data showed that the altered expression levels of lncRNAs AOC4P , PRNCR1 , and PCAT1 might be occurred through the function of demographic and reproductive variables. Taken together, the altered regulation of AOC4P , PRNCR1 , and PCAT1 may highlight their crucial roles in BC development and pathogenesis. Our findings also proposed demographic and reproductive variables as risk factors in BC through the possible influence on the expression of the studied lncRNAs. Nevertheless, further explorations are required to elucidate the more detailed functions of these lncRNAs in BC. [ABSTRACT FROM AUTHOR]

The failure of hair follicle regeneration is the major cause of alopecia, which is a highly prevalent disease worldwide. Dermal papilla (DP) cells play important role in the regulation of hair follicle regeneration. However, the molecular mechanism of how dermal papilla cells direct follicle regeneration is still to be elucidated. In vitro DP 3D culturing and in vivo nude mice DP sphere implanted models were used to examine the molecular regulation of DP cells and follicle regeneration. qRT-PCR and Western blotting were used to detect gene and protein expression, respectively. Immunofluorescence was used to detect the expression level of Wnt10b, Ki-67 and β-catenin. Luciferase assay was used to examine the relationship among PCAT1, miR-329 and Wnt10b. ALP activity was measured by ELISA. H&E staining was used to measure follicle growth in skin tissues. Up-regulation of PCAT1 and Wnt10b, however, down-regulation of miR-329 were found in the in vitro 3D dermal papilla. Bioinformatics analysis and luciferase assays demonstrated that PCAT1 promoted Wnt10b expression by sponging miR-329. Knockdown of PCAT1 suppressed the proliferation and activity, as well as ALP and other DP markers of DP cells by targeting miR-329. Knockdown of PCAT1 regulated miR-329/Wnt10b axis to attenuate β-catenin expression and nucleus translocation to inhibit Wnt/β-catenin signaling. Furthermore, knockdown of PCAT1 suppressed DP sphere induced follicle regeneration and hair growth in nude mice. PCAT1 maintains characteristics of DP cells by targeting miR-329 to activating Wnt/β-catenin signaling pathway, thereby promoting hair follicle regeneration. [ABSTRACT FROM AUTHOR]

The critical roles of long non-coding RNAs (lncRNAs) in the regulation of diverse biological functions has potentiated them as cancer biomarkers. Among these transcripts is the prostate cancer associated transcript 1 (PCAT1) which has been initially shown to exert oncogenic roles in prostate cancer. Further studies revealed its similar roles in various kinds of human malignancies including both solid tumors and hematological malignancies. Animal studies have shown that down-regulation of this lncRNA can attenuate tumor growth in a wide array of cancers including prostate cancer, colorectal cancer, squamous cell carcinoma lung cancer and hepatocellular carcinoma. Studies aimed at identification of diagnostic value of this lncRNA in human cancers reported various values ranging from 0.66 to 0.89 in diverse cancers with the best value reported in multiple myeloma. This lncRNA has a number of putative functional genomic variants such as rs1902432, rs2632159, rs1026411, rs710886, rs16901904 and rs710886 which can modify expression or function of PCAT1 thus altering the risk of human cancers. Based on aberrant expression of PCAT1 in malignancies of diverse origins, this lncRNA can be regarded as a therapeutic target in a vast array of cancers. Thus, modalities for efficient reduction of its expression would be beneficial for several patients. [ABSTRACT FROM AUTHOR]

This study was designed to illustrate the function and role of PCAT1 in CCA. The relative expression was confirmed by RT-qPCR and western blot. The biological function of PCAT1 was evaluated by CCK8, EdU, colony formation, wound healing, transwell, and subcutaneous tumor formation assays. Protein levels of EMT markers were measured by western blot. The binding relationship was predicted by JASPAR and starBase. The binding of YY1 to PCAT1 promoter was assessed by ChIP and luciferase reporter. The binding capacity between miR-216a-3p and PCAT1 as well as BCL3 was assessed by luciferase reporter and AGO2-RIP assays. In this study, we found that PCAT1 was up-regulated in CCA tissues and cells, and the PCAT1 overexpression was associated with poor prognosis. Moreover, PCAT1 was assessed as an independent risk factor of prognosis for CCA patients. Amplified PCAT1 was found to promote tumor proliferation, migration, invasion and EMT process, whereas PCAT1 knockdown inhibited these malignant phenotypes. Mechanistically, PCAT1 was predominantly localized in the cytoplasm and competitively bound miR-216a-3p to increase BCL3 expression. In addition, PCAT1 was activated by transcription factor YY1. This study revealed that PCAT1 acted as an oncogene in CCA, and the YY1/PCAT1/miR-216a-3p/BCL3 axis exhibited critical functions in CCA progression., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Clear cell renal cell carcinoma (ccRCC) is the most common RCC subtype with high metastasis, poor prognosis and conventional chemotherapy resistance. Prostate cancer associated transcript 1 (PCAT1) is an important lncRNA that was reported to be involved in cell proliferation, migration and invasion of several types of cancer cells. However, its role in ccRCC is still undetermined. This study found that PCAT1 levels were elevated in ccRCC tumors as well as several ccRCC cells, and knockdown of PCAT1 with siRNA (si-PCAT1) alleviated cell proliferation, migration and invasion of Caki-2 and ACHN cells. With bioinformatics analysis, dual-luciferase reported assay, RNA pull-down assay and Spearman's correlation analysis, we demonstrated that PCAT1 acted as a sponge for miR-656 and miR-539. Moreover, we found dual competitive interaction of miR-656/539 with PCAT1 and yes-associated protein (YAP), resulting in the identification of PCAT1-miR-656/539-YAP axis in Caki-2 and ACHN cells. With CCK-8 assay and transwell assay, miR-656/539 inhibitor or YAP overexpression could alleviate the effects of si-PCAT1 on the proliferation, migration and invasion of Caki-2 and ACHN cells. Our data indicated that PCAT1 promotes proliferation, migration and invasion of ccRCC cells by upregulating YAP via sponging miR-656 and miR-539. Taken together, this study provided a novel therapeutic target for ccRCC treatment.

MiR-145 has been shown to suppress cell invasiveness and proliferation in endometriosis, whereas prostate cancer-associated transcript 1 (PCAT1) was reported to act as a sponge of miR-145 with one single-nucleotide polymorphism (SNP), rs710886, located in the chromosomal segment of PCAT1. Therefore, this study aimed to explore the association between rs710886 SNP and the risk of endometriosis, as well as the effect of this SNP on the activation of the signaling pathway downstream of PCAT1. Real-time polymerase chain reaction (PCR) was performed to observe the expression of miR-145 in transfected cells, while Matrigel invasion chamber assays and MTT assay were conducted to examine the invasiveness/proliferation among different cell groups. Moreover, bioinformatics tools, luciferase assays, real-time PCR, and Western blot analysis were used to measure the expression of these target genes in the presence of miR-145. Finally, a statistical analysis was conducted to compare the genotypes of rs710886 SNP between fertile healthy women and infertile women with endometriosis. PCAT1 small interfering RNA (siRNA) evidently increased the expression of miR-145 but reduced the invasiveness/proliferation of cells. P-PCAT1 exhibited an opposite effect as that of PCAT1 siRNA, indicating PCAT1 could promote the proliferation and invasiveness of endometriosis stem cells via inhibiting the expression of miR-145. Meanwhile, FASCIN1, SOX2, MSI2, SERPINE1, and JAM-A were identified as target genes of miR-145 via computational analysis and luciferase assays. Finally, a significant genetic effect was observed in both the dominant (AG+GG vs AA) and recessive models (GG vs AG+AA), indicating the presence of an association between the genotype of SNP rs710886 and the risk of endometriosis. SNP rs710886 A>G could lower the expression of PCAT1, thus leading to the overexpression of miR-145. Highly expressed miR-145 would inhibit the invasiveness and proliferation of endometriosis stem cells via targeting specific genes, thus decreasing the risk of endometriosis., (© 2019 Wiley Periodicals, Inc.)

Background: Single-nucleotide polymorphisms (SNPs) in lncRNAs could be biomarkers for susceptibility to colorectal cancer (CRC), but the association of PCAT1 polymorphisms and CRC susceptibility is yet to be studied. Methods: Five tagSNPs covering the PCAT1 gene were detected through Kompetitive Allele-Specific PCR among 436 CRC patients and 510 controls. An expression quantitative trait locus (eQTL) bioinformatic analysis was then performed. Results: In the present study, PCAT1 rs2632159 polymorphism increased CRC risk by 1.37-fold and 2.19-fold in the dominant and recessive models, respectively ( P =0.040 and 0.041). When the CRC cases were divided into colon cancer and rectal cancer, we found that this polymorphism affected colon cancer risk under the dominant model ( P =0.022, OR = 1.51) and affected rectal cancer susceptibility under the recessive model ( P =0.009, OR = 3.03). A more pronounced effect was observed in the male subgroup in that PCAT1 rs2632159 SNP increased rectal cancer risk by 3.97-fold ( P =0.017). When PCAT1 rs2632159 was present, epistatic effects were observed with rs1902432 and rs785005 ( P =0.011 and 0.008, respectively). eQTL analysis showed that rs2632159 could influence binding with the transcription factors EBF, LUN-1, and TCF12. Conclusion: PCAT1 rs2632159 SNP could be a biomarker for CRC risk. And the rs1902432 SNP might only have potential to be a biomarker for colon cancer risk., (© 2019 The Author(s).)

Although colorectal cancer (CRC) is the third most frequent cause of cancer related death in Europe, clinically relevant biomarkers for therapy guidance and prognosis are insufficiently reliable. Long non-coding RNAs (lncRNAs) are RNAs over 200 nucleotides long that are not translated into proteins but can influence biological processes. There is emerging evidence for their involvement in solid cancer as oncogenes, tumour suppressors or regulators of cell proliferation and metastasis development. The goal of this study was to evaluate the prognostic effect of selected lncRNAs in a retrospective study on CRC patients from the Czech Republic. We used a quantitative PCR approach to measure the expression in paired non-malignant and tumour tissue samples of CRC patients of nine lncRNAs previously shown to be involved in cancer progression—ANRIL, CCAT1, GAS5, linc-ROR, MALAT1, MIR155HG, PCAT1, SPRY4-IT1 and TUG1. Associations between expression and expression ratios and clinical characteristics and survival were assessed by using univariable Cox proportional hazards models, Kaplan-Meier estimations with the Gehan-Wilcoxon test, the Mann-Whitney U test, the Kruskal-Wallis test and Spearman's correlations. A comparison of expression in tumour tissue (TT) and non-malignant mucosa tissue (MT) showed significant upregulation of CCAT1 and linc-ROR in TT (p < 0.001 and p = 0.001, respectively) and downregulation of ANRIL, MIR155HG and MALAT1 (p = 0.001, p = 0.010, p = 0.001, respectively). Linc-ROR was significantly associated with the presence of synchronous metastases (p = 0.033). For individual tissue types, lower MIR155HG expression in TT was correlated with both shorter overall survival (p = 0.008) and shorter disease-free survival (p = 0.040). In MT, expression ratios of CCAT1/ANRIL and CCAT1/MIR155HG were associated with overall survival (p = 0.005 and p = 0.006, respectively). Our results revealed that changes in expression of lncRNAs between MT and TT hold potential to be used as prognostic biomarkers in CRC patients. Moreover, the ratios of CCAT1 to ANRIL and MIR155HG in MT also exhibit potential for prognosis assessment without tumour sampling. Our results also indicate that cancer progression is associated with detrimental system-wide changes in patient tissue, which might govern patient survival even after successful elimination of tumour or cancerous cells. [ABSTRACT FROM AUTHOR]

Emerging evidence has showed that lncRNAs and trait-associated loci in lncRNAs play a crucial role in the progression of cancer including prostate cancer (PCa).This study aimed to investigate the molecular mechanisms of lncRNA PCAT1 involved in PCa development and its genetic variant associated with PCa risk. We applied cell proliferation and apoptosis assays to assess the effect of PCAT1 on PCa cell phenotypes. In addition, the genome-wide profiling of gene expression was assessed from three pairs of DU145 cells transfected with PCAT1 overexpression vector or negative control (NC) vector. Furthermore, a case-control study was conducted to explore the associations of four tagging single nucleotide polymorphisms (tagSNPs) and PCa risk in 850 PCa cases and 860 cancer-free controls. Our results showed that lncRNA PCAT1 promoted cell proliferation and inhibited cell apoptosis. Ingenuity pathway analysis (IPA) indicated that dysregulated mRNAs induced by overexpression of PCAT1 were primarily enriched in androgen-independent prostate tumor term and implicated in the disease and functions networks, such as cell death and survival, cell proliferation and gene expression. Besides, rs1902432 in PCAT1 was significantly associated with increased risk of PCa (Additive model: OR = 1.19, P = 0.014; Co-dominant model: CC vs. TT, OR = 1.45, P =0.012; Recessive model: CC vs. TT/CT, OR= 1.34, P = 0.027). This study suggests that PCAT1 may act as an oncogene through promoting cell proliferation and suppressing cell apoptosis in PCa development, and genetic variant in PCAT1 contributes to the susceptibility to PCa., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Long non-coding RNA (lncRNA) is a group of RNAs with broad biogenesis, which are longer than 200 nt and highly conserved in their secondary and tertiary structures. lncRNA that broadly participates in varied physiological processes in organisms has abundant biological function and can regulate expression of target genes at transcriptional, post-transcriptional and epigenetic levels. LncRNAs can also affect the development of diseases, and therefore be used to diagnose and treat diseases. With new sequencing and microarray techniques, hundreds of lncRNAs involved in reproductive disorders have been identified, but their functions in these disorders are undefined. In this paper, we reviewed the studies on how lncRNAs participate in the development of reproductive disorders, hoping our outcome can instruct the future study and provide new biomarkers and therapies for reproductive disorders., Competing Interests: None.

Recent advances in sequencing technology have dramatically improved the ability of investigators to study nucleic acid biology. Bolstered by these new and powerful techniques, the field of noncoding RNA (ncRNA) research, in particular, has witnessed a period of significant progress, wherein multiple new and unique species of ncRNA elements have been discovered and characterized. The current categories of ncRNAs include tRNA, rRNA, snoRNA, snRNA, piRNA, miRNA, and lncRNA, among others. The largest of these RNAs are the long noncoding RNAs (lncRNAs) that perform a diverse set of functions within the cell. Importantly, lncRNAs have recently been implicated in the pathogenesis of multiple types of cancer, including breast, lung, gastric, liver, and prostate. This reviews the major lncRNAs currently believed to play a role in human malignancies with a special emphasis on lncRNAs germane to cancer of the prostate gland. Continued investigation of lncRNA will likely prove to be exceedingly valuable, as they may provide novel therapeutic targets for the treatment of cancer. In addition, lncRNAs offer the potential to serve as diagnostic and prognostic biomarkers for cancer. The present state of lncRNA-based strategies for use in the management of cancer will also be highlighted., (Copyright © 2016 Elsevier Inc. All rights reserved.)