Prostate Androgen-regulated Transcript 1 Research Articles

LncRNA PART1 Attenuates Myocardial Ischemia-Reperfusion Injury by Regulating TFAP2C/DUSP5 Axis via miR-302a-3p.

Myocardial ischemia-reperfusion injury (MIRI) refers to the damage of cardiac function caused by restoration of blood flow perfusion in ischemic myocardium. However, long non-coding RNA prostate androgen regulated transcript 1 (PART1)'s role in MIRI remain unclear. Immunofluorescence detected LC3 expression. Intermolecular relationships were verified by dual luciferase reporter assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry and transferase-mediated dUTP nick-end labeling (TUNEL) assays analyzed cell viability and apoptosis. The release of lactate dehydrogenase was tested via enzyme-linked immunosorbent assay (ELISA). Left anterior descending coronary artery surgery induced a MIRI mouse model. Infarct area was detected by 2,3,5-triphenyltetrazolium chloride staining. Hematoxylin and eosin staining examined myocardial injury. ELISA evaluated myocardial marker (creatine kinase MB) level. PART1 was decreased in hypoxia/reoxygenation (H/R) induced AC16 cells and MIRI mice. PART1 upregulation attenuated the increased levels of Bax, beclin-1 and the ratio of LC3II/I, and enhanced the decrease of Bcl-2 and p62 expression in H/R-treated cells. PART1 upregulation alleviated H/R-triggered autophagy and apoptosis via miR-302a-3p. Mechanically, PART1 targeted miR-302a-3p to upregulate transcription factor activating enhancer-binding protein 2C (TFAP2C). TFAP2C silencing reversed the protected effects of miR-302a-3p inhibitor on H/R treated AC16 cells. We further established TFAP2C combined to dual-specificity phosphatase 5 (DUSP5) promoter and activated DUSP5. TFAP2C upregulation suppressed H/R-stimulated autophagy and apoptosis through upregulating DUSP5. Overexpressed PART1 reduced myocardial infarction area and attenuated MIRI in mice. PART1 improved the autophagy and apoptosis in H/R-exposed AC16 cells through miR-302a-3p/TFAP2C/DUSP5 axis, which might provide novel targets for MIRI treatment.

LncRNA PART1 Regulates Ovarian Carcinoma Development via the miR-150-5p/MYB Axis.

Over the past few years, there have been many reports on the abnormal expression and functional relevance of long non-coding RNAs (lncRNAs) in tumors. The role played by lncRNAs in epithelial ovarian carcinoma (EOC) remains poorly understood, however the goal of the present work was to study molecular mechanisms that underlie involvement of prostate androgen-regulated transcript 1 (PART1) lncRNA in EOC development. A total of 25 tumor and 17 normal specimens were obtained from women undergoing surgery between 2015 and 2019 in the Second Affiliated Hospital, Nanjing Medical University. Expression levels for PART1 in EOC tissue and EOC cell lines were assessed using qRT-PCR. Assays for CCK-8, trans-well, colony forming and western blotting were used to investigate PART1, miR-150-5p and MYB (MYB proto-oncogene) for their invovement in EOC cell proliferation, migration and invasion. Luciferase reporter gene assay was also performed to investigate biological functions of PART1, miR-150-5p and MYB in EOC, and an animal xenograft model was employed to test tumorigenicity. PART1 expression was increased in EOC relative to normal cells and correlated with EOC cell proliferation, migration and invasion. PART1 can sponge miR-150, thereby inhibiting growth of EOC by targeting MYB. The xenograft mouse model revealed that PART1 can regulate tumorigenesis in vivo. The PART1/miR-150/MYB axis is involved in EOC pathogenesis and could represent a new target to use in diagnosis and therapy.

A review on the role of long non-coding RNA prostate androgen-regulated transcript 1 (PART1) in the etiology of different disorders.

LncRNA prostate androgen-regulated transcript 1 (PART1) is an important lncRNA in the carcinogenesis whose role has been firstly unraveled in prostate cancer. Expression of this lncRNA is activated by androgen in prostate cancer cells. In addition, this lncRNA has a role in the pathogenesis intervertebral disc degeneration, myocardial ischemia-reperfusion injury, osteoarthritis, osteoporosis and Parkinson's disease. Diagnostic role of PART1 has been assessed in some types of cancers. Moreover, dysregulation of PART1 expression is regarded as a prognostic factor in a variety of cancers. The current review provides a concise but comprehensive summary of the role of PART1 in different cancers and non-malignant disorders.

The lncRNA prostate androgen-regulated transcript 1 (PART-1) promotes non-small cell lung cancer progression by regulating the miR-204-3p/IGFBP-2 pathway

Abstract Objectives Lung cancer is a common malignant tumour of the lung and the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for 80–85% of lung cancers, and 40% of NSCLCs have spread beyond the lungs by the time they are diagnosed. The long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART-1) has been reported to promote the development of several cancers. Methods In the current study, we investigated the role of PART-1 in the proliferation, invasion, and migration of NSCLC. Results The expression levels of the PART-1 gene were higher in NSCLC cell lines, including A549, H1229, H1650, H1975, and PC9, than in human bronchial epithelia (HBE) cell lines. Knocking down PART-1 inhibited the proliferation, invasion, and migration of A549 cells and decreased tumour proliferation in nude mice. We confirmed that PART-1 targeted miR-204-3p directly and that miR-204-3p targeted insulin-like growth factor binding protein 2 (IGFBP-2) directly. Furthermore, we discovered that PART-1 impacts NSCLC progression by regulating the miR-204-3p-targeted IGFBP-2 pathway. Conclusions The lncRNA PART-1 might be a target for treating NSCLC and an early marker in the diagnosis of early lung cancer.

Long non‑coding RNA PART1: dual role in cancer.

Increasing evidence has shown that long non-coding RNAs (lncRNAs), which are non-coding endogenous single-stranded RNAs, play an essential role in various physiological and pathological processes through transcriptional interference, post-transcriptional regulation, and epigenetic modification. Moreover, lncRNAs, as oncogenes or tumor suppressor genes, play an important role in the occurrence and development of human cancers. Prostate androgen-regulated transcript 1 (PART1) was initially identified as a carcinogenic lncRNA in prostate adenomas. The upregulated expression of PART1 plays a tumor-promoting role in liver, prostate, lung cancers, and other tumors. In contrast, the expression of PART1 is downregulated in esophageal squamous cell carcinoma, glioma, and other tumors, which may inhibit the tumor. PART1 plays a dual role in cancer and regulates cell proliferation, apoptosis, invasion, and metastasis through a variety of potential mechanisms. These findings suggest that PART1 is a promising tumor biomarker and therapeutic target. This article reviews the biological functions, related mechanisms, and potential clinical significance of PART1 in a variety of human cancers.

LncRNA PART1 Stimulates the Development of Ovarian Cancer by Up-regulating RACGAP1 and RRM2.

Ovarian cancer (OC) is a kind of gynecologic malignancy with a high mortality rate. Long non-coding RNAs (lncRNAs) have been reported to exert regulatory roles in multiple diseases. However, the role of lncRNA prostate androgen-regulated transcript 1 (PART1) has not been investigated in the development of OC. In this study, from RT-qPCR analysis, we discovered that PART1 demonstrated high expression in OC cells. Moreover, data from functional assays manifested that PART1 reduction hindered the proliferative, migratory, and invasive capabilities of OC cells. In vivo uncovered that PART1 knockdown impeded OC tumor growth. Furthermore, from the experimental results of RNA pull down, RIP, and luciferase reporter assays, we discovered that PART1 served as a sponge for microRNA-6884-5p (miR-6884-5p) to modulate the expression of Rac GTPase activating protein 1 (RACGAP1) and ribonucleotide reductase regulatory subunit M2 (RRM2). Finally, rescue assays proved that overexpression of RACGAP1 or RRM2 abrogated the suppressive role of PART1 knockdown on OC cell malignant behaviors. RACGAP1 and RRM2 were also revealed to act as oncogenes in OC cells. In summary, our research verified the PART1/miR-6884-5p/RACGAP1/RRM2 axis in OC cells, which signified that PART1 might act as a novel biomarker in OC.

Repression of lncRNA PART1 attenuates ovarian cancer cell viability, migration and invasion through the miR-503-5p/FOXK1 axis

BackgroundOvarian cancer (OC) is a female malignant tumor with a high fatality rate. Long non-coding RNAs (lncRNAs) are deeply involved in OC progression. The aim of this study is to explore the specific mechanism of lncRNA prostate androgen-regulated transcript 1 (PART1) in OC.MethodsQuantitative real time PCR was utilized to determine the expression levels of PART1, microRNA (miR)-503-5p and forkhead-box k1 (FOXK1) in OC tissues and/or cells. The cell viability, migration, and invasion in OC were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide assay, wound healing assay and transwell invasion assay, respectively. Flow cytometry was used to analyze the cell apoptosis. The xenograft tumor was conducted in nude mice to verify the effect of PART1 knockdown on OC in vivo. The target relationships among PART1, miR-503-5p and FOXK1 were predicted by StarBase, and verified by luciferase reporter assay. The level of FOXK1 was assessed by western blot.ResultsIncreased expression of PART1 and FOXK1 was observed in OC tissues or cells, whereas miR-503-5p was downregulated. PART1 silencing or miR-503-5p overexpression repressed the cell viability, migration and invasion, and protomed apoptosis. Meanwhile, miR-503-5p was a target of PART1, and FOXK1 was a direct target gene of miR-503-5p. Both downregulation of miR-503-5p and upregulation of FOXK1 partly relieved the suppressive effects of PART1 knockdown on the oncogenicity of OC in vitro.ConclusionDecreased PART1 represses the cell viability, migration and invasion of OC via regulating the miR-503-5p/FOXK1 axis, which provided an underlying target for treating OC.

Downregulation of PART1 Inhibits Proliferation and Differentiation of Hep3B Cells by Targeting hsa-miR-3529-3p/FOXC2 Axis.

Background Long noncoding RNAs (lncRNAs) are an important subtype of noncoding RNAs (ncRNAs) and microRNA sponges regulate protein-coding gene expression. The lncRNA prostate androgen-regulated transcript 1 (PART1) was implicated in the process of several cancer pathogeneses. However, studies on the regulation of PART1 expression and its mechanism in liver cancer are lacking. Methods qRT-PCR and western blot were used to detect PART1 levels in liver cancer serums and cell lines. Cell proliferation, migration, and invasion were detected using CCK8 assays, cell clones, and transwell assays. Interaction between PART1 and miR-3529-3p and forkhead box protein C2 (FOXC2) was confirmed using dual-luciferase reporter assays. Results We revealed that expression levels of PART1 and FOXC2 are significantly upregulated and the miR-3529-3p expression level significantly decreases in the serum while high expression level of PART1 is positively associated with tumour size, BCLC stage, and TNM stage. shRNA of PART1 can significantly reduce the ability of cell migration and invasion by regulating AKT signalling associated with the reduction of MMP-2 and MMP-9 protein expression. Dual-luciferase reporter assays showed that PART1 can sponge miR-3529-3p, which targets FOXC2 in liver cancer cells. The promoting or suppressing effect of PART1 for Hep3B cell proliferation, invasion, and migration is revised by miR-3529-3p mimics and inhibitors. Conclusion Results showed that downregulation of PART1 can partially inhibit proliferation and differentiation by targeting hsa-miR-3529-3p/FOXC2 axis.

LncRNA PART1 Promotes Proliferation and Migration, Is Associated with Cancer Stem Cells, and Alters the miRNA Landscape in Triple-Negative Breast Cancer.

Simple SummaryLong non-coding RNAs (lncRNAs) play an important role in cancer progression. Herein we provide new information regarding the role of prostate androgen regulated transcript 1 (PART1). We show that the lncRNA PART1 is enriched in triple-negative breast cancers and cancer stem cell populations. We demonstrate its role in cancer cell and tumor growth and provide evidence for its association with worse survival in a subset of breast cancer patients. Importantly, our genome-wide analyses have revealed novel insights into the function of this lncRNA, demonstrating how it changes the microRNA (miRNA) landscape leading to genome-wide mRNA expression regulation. Our study suggests that PART1 represents an attractive target for the treatment of triple-negative breast cancers.Triple-negative breast cancers (TNBCs) are aggressive, lack targeted therapies and are enriched in cancer stem cells (CSCs). Novel therapies which target CSCs within these tumors would likely lead to improved outcomes for TNBC patients. Long non-coding RNAs (lncRNAs) are potential therapeutic targets for TNBC and CSCs. We demonstrate that lncRNA prostate androgen regulated transcript 1 (PART1) is enriched in TNBCs and in Aldefluorhigh CSCs, and is associated with worse outcomes among basal-like breast cancer patients. Although PART1 is androgen inducible in breast cancer cells, analysis of patient tumors indicates its androgen regulation has minimal clinical impact. Knockdown of PART1 in TNBC cell lines and a patient-derived xenograft decreased cell proliferation, migration, tumor growth, and mammosphere formation potential. Transcriptome analyses revealed that the lncRNA affects expression of hundreds of genes (e.g., myosin-Va, MYO5A; zinc fingers and homeoboxes protein 2, ZHX2). MiRNA 4.0 GeneChip and TaqMan assays identified multiple miRNAs that are regulated by cytoplasmic PART1, including miR-190a-3p, miR-937-5p, miR-22-5p, miR-30b-3p, and miR-6870-5p. We confirmed the novel interaction between PART1 and miR-937-5p. In general, miRNAs altered by PART1 were less abundant than PART1, potentially leading to cell line-specific effects in terms miRNA-PART1 interactions and gene regulation. Together, the altered miRNA landscape induced by PART1 explains most of the protein-coding gene regulation changes (e.g., MYO5A) induced by PART1 in TNBC.

Long non-coding RNA PART1 predicts a poor prognosis and promotes the malignant progression of pancreatic cancer by sponging miR-122

Background and objectivesLong non-coding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) was previously shown to exert an oncogenic role in several human cancers. However, whether PART1 is associated with the malignant progression of pancreatic cancer remains unclear. In the current study, we aimed to identify the role and potential mechanism of PART1 in pancreatic cancer.MethodsqRT-PCR was applied to detect PART1 expression in 45 cases of pancreatic cancer patients. The chi-square test was performed to assess the association between PART1 expression and clinicopathologic features, and Kaplan-Meier method was applied to evaluate overall survival. In vitro CCK-8, transwell invasion, and flow cytometry assays were applied to detect the effects of PART1 on cell proliferation, invasion, and apoptosis, respectively. Luciferase reporter and RNA immunoprecipitation assays were used to identify the regulatory mechanism between PART1 and miR-122.ResultsPART1 expression was upregulated in pancreatic cancer tissues and cell lines. High PART1 expression was closely correlated with tumor size, T classification, clinical stage, and vascular invasion, and predicted a poor overall survival. PART1 knockdown significantly suppressed cell proliferation and invasion abilities of pancreatic cancer but promoted cell apoptosis. PART1 was found to serve as a molecular sponge of miR-122, and miR-122 inhibition partially reversed the inhibitory phenotypes of PART1 knockdown on pancreatic cancer cells.ConclusionsPART1 promotes the malignant progression of pancreatic cancer by sponging miR-122. The PART1/miR-122 axis might be a promising target for anticancer therapy in patients with pancreatic cancer.

LncRNA PART1, manipulated by transcriptional factor FOXP2, suppresses proliferation and invasion in ESCC by regulating the miR‑18a‑5p/SOX6 signaling axis.

An increasing number of studies have demonstrated that long non-coding (lnc)RNAs are associated with tumor invasion, metastasis and the prognosis of patients with a variety of different tumors. However, the roles of lncRNA prostate androgen regulated transcript 1 (PART1) in esophageal squamous cell carcinoma (ESCC) remain unknown. In the present study, reverse transcription-quantitative PCR was performed to investigate the levels of PART1, SRY-box transcription factor 6 (SOX6) and miR-18a-5p in ESCC tissues and cells. The functions of PART1 in ESCC were demonstrated using Cell Counting Kit-8 and Matrigel assays. Promoter activity and dual-luciferase reporter assays, RNA immunoprecipitation and western blot analyses were also used to determine the potential mechanisms of PART1 in ESCC cell lines. It was found that PART1 and SOX6 were both downregulated in ESCC tissues and cells, and their low expression levels were associated with TNM stage, lymph node metastasis and poor prognosis in patients with ESCC. Forkhead box protein P2 (FOXP2) exhibited low expression level in ESCC tissues, and its expression was positively correlated with PART1 expression level in ESCC tissues. FOXP2 was found to bind to the promoter region of PART1 to regulate its expression in ESCC cells. Functionally, PART1 overexpression suppressed cell proliferation and invasion, whereas PART1 downregulation promoted cell proliferation and invasion in the ESCC cell lines. Mechanistically, PART1 functions as a competing endogenous (ce)RNA by sponging miR-18a-5p, resulting in the upregulation of the downstream target gene, SOX6, coupled with the inactivation of the β-catenin/c-myc signaling axis, to suppress ESCC cell proliferation and invasion. In conclusion, data from the present study unveil a potential ceRNA regulatory pathway, in which PART1 affects SOX6 expression level by sponging miR-18a-5p, to ultimately suppress ESCC development and progression.

Role of lncRNA PART1 in intervertebral disc degeneration and associated underlying mechanism.

Intervertebral disc degeneration (IDD) is a chronic skeletal muscle degeneration disease. Previous studies have demonstrated that long non-coding RNAs (lncRNAs) exert significant roles in serious illnesses. Prostate androgen-regulated transcript 1 (PART1) is an identified lncRNA that has been reported to be a regulator in a number of diseases. However, the potential effects of PART1 in IDD have yet to be fully elucidated. The present study aimed to investigate the roles of lncRNA PART1 in IDD and identify a possible underlying mechanism. Human nucleus pulposus (NP) cells were first exposed to lipopolysaccharide (LPS) to construct in vitro IDD models. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure lncRNA PART1 expression levels in 10 ng/ml LPS-stimulated NP cells and normal cells (untreated cells). Dual-luciferase reporter assays were conducted to verify the possible binding sites of microRNA (miR)-190a-3p on lncRNA PART1. In addition, NP cell viability and apoptosis were measured by performing MTT and flow cytometry, respectively. Expression and secretion of inflammatory factors (TNF-α, IL-1β and IL-6) and extracellular matrix (ECM) degradation-related proteins (aggrecan and collagen type II) were measured using ELISA, RT-qPCR and western blotting. Expression levels of lncRNA PART1 in LPS-treated NP cells were found to be higher compared with those in the control groups. miR-190a-3p directly targeted lncRNA PART1. PART1 knockdown enhanced cell viability, reduced cell apoptosis, inhibited inflammatory factor secretion and promoted ECM degradation in LPS-stimulated NP cells. However, transfection with the miR-190a-3p inhibitor reversed the aforementioned PART1 knockdown-induced alterations in cell viability, apoptosis, inflammatory cytokine and ECM degradation. Collectively, these results suggest that PART1 accelerates the progression of IDD by directly targeting miR-190a-3p, which provides a novel target for IDD diagnosis and treatment.

Long noncoding RNA PART1 restrains aggressive gastric cancer through the epigenetic silencing of PDGFB via the PLZF-mediated recruitment of EZH2.

Current reports refer to the role of long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) as a tumor suppressor in some types of cancer but as an oncogene in other kinds of cancer. In gastric cancer, it had been reported to be downregulated. However, the clinical significance and underlying mechanism of PART1 function in gastric cancer remains undefined. Here, seven differential expression levels of noncoding RNAs (DE-lncRNAs) were screened from gastric cancer through a probe reannotation of a human exon array. PART1 was selected for further study because of its high fold change number. In our cohort, PART1 was identified as a significant downregulated lncRNA in gastric cancer tissues by qPCR and in situ hybridization (ISH), and its low expression was significantly correlated with postoperative metastasis and short overall survival time after surgery. Through the results of gain-of-function experiments, PART1 was confirmed as a tumor suppressor that can decrease not only cell viability, migration, and invasion in vitro but also tumorigenesis and tumor metastasis in vivo. Mechanistically, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) showed that PART1 interacts with androgen receptor (AR), and then, promyelocytic leukemia zinc finger (PLZF) is upregulated in an androgen-independent manner. In a chain reaction, chromatin immunoprecipitation (ChIP) assay additionally illustrated that PLZF upregulation increased the enrichment of EZH2 and H3K27 trimethylation in the platelet-derived growth factor (PDGFB) promotor, thereby inhibition of PDGFB and the subsequent PDGFRβ/PI3K/Akt signaling pathway. Based on these findings, we showed PART1 plays a tumor suppressor role by promoting PLZF expression followed by recruitment of EZH2 to mediate epigenetic PDGFB silencing and downstream PI3K/Akt inhibition, suggesting that PART1 has a key role in restraining the aggressive ability of GC cells and providing a novel perspective on lncRNAs in GC progression.

Long Noncoding RNA PART1 Promotes Hepatocellular Carcinoma Progression via Targeting miR-590-3p/HMGB2 Axis.

IntroductionIn East Asia, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancer types. Long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) was reported to play crucial roles in regulating cancer progression. However, roles and mechanisms of action of PART1 in hepatocellular carcinoma (HCC) still remain unknown.MethodsQuantitative real-time polymerase chain reaction (RT-qPCR) method was used to detect the PART1 expression level in HCC cells. Cell proliferation, colony formation, and transwell invasion assays were performed to investigate the biological roles of PART1 on HCC cell behaviors. Bioinformatic analysis methods were performed to analyze connections of microRNA-590-3p (miR-590-3p) with PART1 or high mobility group box 2 (HMGB2) in HCC. Moreover, expression levels of PART1, miR-590-3p, and HMGB2 in HCC tissues and normal tissues were analyzed at ENCORI.ResultsPART1 expression was found to be significantly upregulated in HCC tissues and cells. Functionally, silencing of PART1 significantly suppressed HCC cell proliferation, colony formation and invasion in vitro, while forcing PART1 exerts opposite biological effects. Mechanically, miR-590-3p/HMGB2 axis was downstream target of PART1, and silencing of miR-590-3p or forcing of HMGB2 could rescue the stimulation effects of PART1 overexpression on HCC cell behaviors.DiscussionOur results provided evidence that PART1 serves as oncogenic lncRNA through sponging miR-590-3p to upregulate HMGB2 expression in HCC.

Inhibition of lncRNA PART1 Chemosensitizes Wild Type but Not KRAS Mutant NSCLC Cells.

BackgroundLung cancer has the highest incidence among solid tumors in men and is the third most common cancer in women. Despite improved understanding of genomic and mutational landscape in non-small cell lung cancer (NSCLC), the five-year survival in these patients has remained stagnant at a dismal 15%. The first line of treatment commonly adapted for NSCLC patients with somatic mutation in EGFR is tyrosine kinase inhibitor gefitinib or erlotinib. EGFR mutant cells seem to be intrinsically sensitive to tyrosine kinase inhibitors; however, the remaining 20–30% patients are resistant to tyrosine kinase inhibitor.Materials and MethodsHere we show, using in vitro normal and NSCLS cell lines, that the lncRNA Prostate androgen-regulated transcript 1 (PART1) is expressed at higher levels in NSCLC cells compared to normal lung epithelial cell line, corroborating two earlier studies.ResultsWe additionally show that these cells are resistant to erlotinib which is reversed in some, but not all, cell lines following suppression of PART1 expression. The differential response to erlotinib following siRNA-mediated knockdown of PART1 was found to be related to the mutational status of KRAS. Only in cells with wild-type KRAS suppression of PART1 sensitized them to erlotinib. Knockdown of mutant KRAS did not sensitize those cell lines to erlotinib. But knockdown of mutant KRAS along with suppression of PART1 sensitized the cells to treatment with erlotinib. The results from the study reveal a yet undefined and important role of lncRNA PART1 in defining sensitivity to erlotinib. This action is mediated by mutation status of KRAS.ConclusionEven though preliminary, our results indicate PART1 might be a potential candidate for targeted therapy or used as a predictor of chemosensitivity in patients with NSCLC.

Long Non-Coding RNA PART1 Promotes Proliferation, Migration and Invasion of Hepatocellular Carcinoma Cells via miR-149-5p/MAP2K1 Axis.

BackgroundHepatocellular carcinoma (HCC) is the most common primary hepatic malignancy worldwide. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as effective markers for the detection of multiple cancers. This study aimed to illuminate the mechanism of prostate androgen regulated transcript 1 (PART1) in HCC.Materials and MethodsThe levels of PART1, miR-149-5p and mitogen-activated protein kinase 1 (MAP2K1) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay, and cell migration and invasion were evaluated by transwell assay. Dual-luciferase reporter assay was carried out to examine the relationship among PART1, miR-149-5p and MAP2K1. Western blot assay was conducted to measure the protein expression of MAP2K1.ResultsPART1 and MAP2K1 expression were greatly increased and miR-149-5p level was decreased in HCC tissues. Functional analysis revealed that the si-PART1 inhibited proliferation, migration and invasion of HCC cells. PART1 directly bound to miR-149-5p and miR-149-5p level was down-regulated by PART1. Moreover, restoration experiment demonstrated that the effect of PART1 knockdown on HCC cell progression could be partially rescued by miR-149-5p depletion. MiR-149-5p was predicted to target MAP2K1 and MAP2K1 expression was negatively modulated by miR-149-5p. Also, MAP2K1 rescued the inhibitory effects of miR-149-5p overexpression on proliferation, migration and invasion in HCC cells. Besides, the inhibition of miR-149-5p weakened the impact on MAP2K1 expression mediated by PART1 repression.ConclusionPART1 promoted proliferation, migration and invasion of HCC cells by regulating miR-149-5p/MAP2K1 axis.

Long Non-Coding RNA PART1 Exerts Tumor Suppressive Functions in Glioma via Sponging miR-190a-3p and Inactivation of PTEN/AKT Pathway.

BackgroundGlioma is the most commonly diagnosed primary brain tumor. Dysregulation of long non-coding RNA (lncRNA) is associated with initiation and development of various cancer types including glioma.MethodsThe relative expression of lncRNA was analyzed by real time-quantitative polymerase chain reaction (RT-qPCR). Cell counting kit (CCK-8) and flow cytometry analysis were applied to explore the role of prostate androgen-regulated transcript 1 (PART1) in glioma cell lines. Luciferase reporter assay, Western blotting and RT-qPCR were used to investigate the association between PART1, miR-190a-3p and phosphatase and tensin homolog deleted on chromosome ten (PTEN) in glioma cell lines.ResultsIn the present study, we elucidated a pivotal role and molecular mechanism of lncRNA PART1 in glioma cell lines. It was found that PART1 was significantly downregulated in glioma tissues compared to normal tissues according to TCGA data and our RT-qPCR results. The cell-based assays showed that PART1 suppressed cell proliferation and triggered cell apoptosis in glioma cell lines. PART1 inactivated PI3K/AKT cascade in glioma cell lines. Transfection of constitutively activated AKT (Myr-AKT) reversed PART1 induced cell apoptosis and cell growth arrest. The bioinformatic analysis suggested that miR-190a-3p might bind to PART1. In the dual luciferase reporter assay, we validated that PART1 directly bound to miR-190a-3p in glioma cell lines. Furthermore, there was a reciprocal repression between PART1 and miR-190-3p. In addition, PART1 upregulated PTEN and inactivated PI3K/AKT pathway in glioma cell lines. Moreover, silencing of PTEN reversed PART1 overexpression induced cell growth arrest and apoptosis. In glioma tissues, the Pearson Correlation analysis showed that there was a strong-positive correlation between PART1 level and PTEN mRNA level.ConclusionTaken together, the current study revealed a PART1/miR-190a-3p/PTEN/PI3K/AKT axis in glioma and provided novel insights for understanding the complex lncRNA-miRNA network in glioma.

LncRNA PART1 facilitates the malignant progression of colorectal cancer via miR-150-5p/LRG1 axis.

Study has shown that long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) was elevated in colorectal cancer tissues and cells, and the proliferation and metastasis of colorectal cancer cells were reduced after its downregulation. The tumor-suppressive role of microRNA-150-5p (miR-150-5p) has been shown in colorectal cancer. In this study, the association between PART1 and miR-150-5p in colorectal cancer was analyzed. Results revealed an increase of PART1, but a decrease of miR-150-5p in 56 colorectal cancer tissues. And there was a strong negative correlation between levels of PART1 and miR-150-5p in these cancer samples. Also, compared with 10 healthy controls, the level of PART1 was increased, whereas miR-150-5p expression was diminished in the serum of 10 colorectal cancer patients. Cell proliferation and migration, along with epithelial-mesenchymal transition, was promoted by PART1 overexpression. However, this lncRNA mitigated apoptosis of colorectal cancer cells. Whereas miR-150-5p mimic abrogated these effects caused by PART1 overexpression. The influences of PART1 knockdown on the above malignant characteristics of colorectal cancer cells were contrary to its overexpression. miR-150-5p inhibitor ablated the effects induced by PART1 knockdown. In xenograft mouse models, silencing of PART1 decreased tumor volume and weight. Our data supported that lncRNA PART1 may regulate leucine-rich α-2-glycoprotein-1 (LRG1) expression through a competing interaction mechanism that hindering miR-150-5p function. In conclusion, PART1 facilitates the malignant progression of colorectal cancer via miR-150-5p/LRG1 pathway. The study further clarified the molecular mechanism of PART1 in colorectal cancer. This study may provide a new approach to diagnose and treat colorectal cancer.

LncRNA PART-1 targets TGFBR2/Smad3 to regulate cell viability and apoptosis of chondrocytes via acting as miR-590-3p sponge in osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease that commonly occurs in the elderly. This study focused on apoptosis and explored the modulating effects of long non‐coding (lncRNAs) prostate androgen‐regulated transcript‐1 (PART‐1) on chondrocytes apoptosis. In the present study, the PART‐1 expression level was down‐regulated in the OA cartilages. Silence of PART‐1 decreased the cell viability and promoted chondrocytes apoptosis. Overexpression of PART‐1 could reverse the effects induced by interleukin 1β (IL‐1β) stimulation, thus slowing down the apoptosis rate. MiR‐590‐3p was found to be the potential target, and RNA immunoprecipitation and luciferase activity assay confirmed the binding between PART‐1 and miR‐590‐3p. Moreover, miR‐590‐3p was down‐regulated by PART‐1 and was negatively associated with PART‐1. Transforming growth factor‐beta receptor type 2 (TGFBR2) was positively associated with PART‐1. Down‐regulation of PART‐1 decreased cell viability and induced cell apoptosis, which was partially reversed by miR‐590‐3p silence or TGFBR2 overexpression; while overexpression of PART‐1 increased the cell viability and decreased the caspase 3 activity and apoptotic rates, and the effects were partially attenuated by miR‐590‐3p overexpression or silence of TGFBR2 in IL‐1β‐stimulated chondrocytes. Knock‐down of PART‐1 down‐regulated both Smad3 and p‐Smad3 protein levels, which was reversed by miR‐590‐3p inhibition or TGFBR2 overexpression. Smad3 expression level was lower in the OA group than that in the normal group and was positively associated with the PART‐1 expression level. Collectively, the study revealed that lncRNA PART‐1 regulates the apoptosis of chondrocytes in OA by acting as a sponge for miR‐590‐3p, which subsequently regulates TGFBR2/Smad3 signalling.

Long noncoding RNA PART1 promotes progression of non-small cell lung cancer cells via JAK-STAT signaling pathway.

Non‐small cell lung cancer (NSCLC), the major type of lung cancer, becomes the greatest threat to the life of people. Growing evidence shows prostate androgen‐regulated transcript 1 (PART1) is considered as effective markers for prostate cancer, and has been shown to be associated with poor prognosis of NSCLC. However, the tumorigenic mechanism of PART1 in NSCLC remains to be investigated. In this study, we found that the expression of PART1 was robustly induced in NSCLC tissues and cell lines. Functional studies established that overexpression of PART1 could promote NSCLC cell proliferation, migration, and invasion, while interference of PART1 inhibited NSCLC progression. Our results also identified miR‐635 as a novel target of PART1, whose expression was inhibited by PART1 in NSCLC cell lines. Moreover, gain‐ and loss‐of‐function studies revealed that PART1 could sponge miR‐635 and increase the expression of Janus kinase (JAK) and signal transducer and activator of transcription proteins (STATs). Finally, we deciphered the molecular mechanism by which PART1 contributed to promotion of NSCLC cell progression via phosphorylation and activation of JAK‐STAT signaling pathway. The animal experiment further confirmed that interference of NSCLC could suppress in vivo tumorigenic ability of NSCLC with favorable pharmacological activity via inactivation of JAK‐STAT signaling pathway. In conclusion, our findings clarified the biologic significance of PART1/miR‐635/JAK‐STAT axis in NSCLC progression and provided novel evidence that PART1 may be a new potential therapeutic target for the treatment of NSCLC.