Long non-coding RNA PlncRNA-1 promotes cell proliferation and hepatic metastasis in colorectal cancer.

Emerging evidence has identified that long non-coding RNAs (lncRNAs) may play an important role in the pathogenesis of many cancer types, including colorectal cancer (CRC). However, the role of PlncRNA-1 in CRC remains unclear. The aim of our present study was to investigate the potential functions of PlncRNA-1 in CRC and to identify the underlying mechanisms of action. We demonstrated that up-regulated PlncRNA-1 in CRC tissues and cells promoted cell proliferation by accelerating cell cycle process and inhibiting cell apoptosis in vitro, enhanced tumor growth and matastasis in vivo and was associated with cell migration and invasion, EMT process of CRC cells. In addition, PlncRNA-1 was a target of miR-204 and enhanced the expression of an endogenous miR-204 target, MMP9 in CRC cells. Furthermore, we found that PlncRNA-1 activates Wnt/ß-catenin pathway through the miR-204 in CRC cells. These results suggest that the PlncRNA-1/miR-204/ Wnt/ß-catenin regulatory network may shed light on tumorigenesis in CRC.

PlncRNA-1 is overexpressed in retinoblastoma and regulates retinoblastoma cell proliferation and motility through modulating CBR3.

PlncRNA-1 has been suggested to function as an oncogenic role in prostate cancer, colorectal cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer. The expression pattern of PlncRNA-1 in retinoblastoma remained unknown. Therefore, the aim of this study was to explore the clinical significance of PlncRNA-1 in retinoblastoma patient and the biological function and molecular mechanism of PlncRNA-1 in regulating retinoblastoma cell proliferation, migration, and invasion. The results showed the level of PlncRNA-1 expression was obviously increased in retinoblastoma tissues and cell lines compared with compared with normal retina tissues and retina cell lines, respectively. Meanwhile, patients with advanced stage retinoblastoma had higher levels of PlncRNA-1 expression than patients with early stage retinoblastoma. There was an inverse correlation between PlncRNA-1 expression and CBR3 expression in retinoblastoma tissues, and PlncRNA-1 negatively regulated mRNA and protein expressions of CBR3. The in vitro experiments showed that down-regulation of PlncRNA-1 expression suppressed retinoblastoma cell proliferation, migration and invasion through up-regulating CBR3. In conclusion, PlncRNA-1 serves as an oncogenic lncRNA in regulating retinoblastoma cell proliferation, migration, and invasion through proliferation, migration, and invasion through up-regulating CBR3. © 2018 IUBMB Life, 70(10):969-975, 2018.

MiR-34c and PlncRNA1 mediated the function of intestinal epithelial barrier by regulating tight junction proteins in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is originated from uncontrolled inflammation, and desired methods for IBD therapy remains the main difficult. The network comprised with miRNA and lncRNA has been verified to play an important role on diverse human diseases. In this study, we demonstrated the role of miR-34c and lncRNA PlncRNA1 on the function of intestinal barrier. METHODS: Intestinal epithelial barrier model was constructed based on normal intestinal epithelial cell line Caco-2. 2% DSS was supplemented in the Apical side of the model cells to induce the injury of intestinal epithelial barrier. Real-time PCR or western blot was used to determine mRNA or protein expression of miR-34c, PlncRNA1, Myc-associated zinc finger protein (MAZ), zonula occludens 1 (ZO-1) and occludin. RESULTS: DSS induced injury of intestinal epithelial barrier, while overexpression of PlncRNA1 seemed to protect intestinal epithelial barrier from injury. Tight junction (TJ) proteins ZO-1 and occludin were regulated by MAZ, while, miR-34c targeted MAZ to regulate its expression, in addition, PlncRNA1 and miR-34c bound together to regulate the expressions of MAZ, ZO-1 and occludin. The protect effects of PlncRNA1 overexpression on intestinal epithelial barrier function was reversed by overexpression of miR-34c. CONCLUSION: MAZ and TJ proteins were involved in the function of intestinal epithelial barrier, while miR-34c and PlncRNA1 regulated the intestinal dysfunction cooperatively.

LncRNA PlncRNA-1 accelerates the progression of prostate cancer by regulating PTEN/Akt axis.

Long non-coding RNAs are key regulators of tumor development and progression, with the potential to be biomarkers of tumors. This study aimed to explore the role of PlncRNA-1 in the progression of prostate cancer (PCa). We found that PlncRNA-1 was up-regulated in 85.29% of PCa tissues and could predict the T stage of PCa patients to a certain extent. Results showed that inhibition of PlncRNA-1 expression potentially promoted cell apoptosis, suppressed the proliferation, migration, and invasion of cells, and triggered G2/M cycle arrest in vitro and in vivo. PlncRNA-1 was mainly localized in the nucleus and PlncRNA-1 expression and phosphatase and tensin homologue (PTEN) expression were negatively correlated. Mechanistically, knockdown of PlncRNA-1 increased expression levels of PTEN protein and phosphorylated PTEN protein, and decreased expression levels of Akt protein and phosphorylated Akt protein. Rescue experiments demonstrated that PTEN inhibitors abolished the changes in PTEN/Akt pathway caused by PlncRNA-1 interference. PlncRNA-1 can promote the occurrence and development of PCa via the PTEN/Akt pathway. PlncRNA-1 may, therefore, be a new candidate target for the treatment of PCa.

LncRNA PlncRNA-1 participates in rheumatoid arthritis by regulating transforming growth factor ß1.

LncRNA PlncRNA-1(PlncRNA-1) participates in breast cancer by upregulating TGF-ß1. It is known that TGF-ß1 plays an inhibitory role in the inflammatory responses in rheumatoid arthritis (RA). Therefore, PlncRNA-1 may also participate in RA. Serum and synovial fibroblasts were obtained from 34 patients with active RA (persistent symptoms), 36 patients with inactive RA (long term of no or few symptoms after active RA) and 40 healthy controls. Expression levels of PlncRNA-1 and TGF-ß1 in active RA patients, inactive RA patients and healthy controls were measured by RT-qPCR and ELISA, respectively. Pearson Correlation Coefficient was used to determine the correlation between the expression levels of PlncRNA-1 and TGF-ß1. Diagnostic value of PlncRNA-1 for active RA was detected by ROC curve analysis. PlncRNA-1 and TGF-ß1 were downregulated in serum of active RA patients but not in inactive RA patients compared to the healthy controls. Expression of PlncRNA-1 and TGF-ß1 were positively correlated only in RA patients, and altered expression levels of PlncRNA-1 distinguished the active RA patients from inactive RA patients and healthy controls. PlncRNA-1 and TGF-ß1 were also downregulated in synovial fibroblasts derived from RA patients in comparison to inactive RA patients and healthy controls. Overexpression of PlncRNA-1 mediated upregulation of TGF-ß1 in synovial fibroblasts derived from RA patients, while exogenous TGF-ß1 treatment showed no significant effect on the expression of PlncRNA-1. Therefore, PlncRNA-1 participated in RA possibly by regulating TGF-ß1.

LncRNA PlncRNA-1 overexpression inhibits the growth of breast cancer by upregulating TGF-ß1 and downregulating PHGDH.

OBJECTIVE: To investigate the role of lncRNA PlncRNA-1 in the pathogenesis of breast cancer. METHODS: A total of 78 patients with breast cancer as well as 48 healthy females were included in this study. Expression in tumor tissues and adjacent healthy tissues of breast cancer patients, as well as in breast tissues and serum of both patients and healthy control was detected by qRT-PCR. Cell proliferation was detected by CCK-8 assay, and cell apoptosis was tested by MTT assay. PlncRNA-1 overexpression cell lines were constructed and the effects on TGF-ß1 as well as phosphoglycerate dehydrogenase (PHGDH) were explored by western blot. RESULTS: Expression levels of PlncRNA-1 were significantly lower in tumor tissues than those in adjacent healthy tissues. Significantly lower expression levels of PlncRNA-1 were also found in breast cancer patients than those in healthy controls in both breast tissue and serum. Upregulation of PlncRNA-1 promoted the expression of TGF-ß1, but inhibited the expression of PHGDH. LncRNA PlncRNA-1 overexpression reduced the proliferation rate, but increased the apoptosis rate of breast cancer cells, while treatment with TGF-ß inhibitor reduced those effects of PlncRNA-1 overexpression. CONCLUSION: LncRNA PlncRNA-1 overexpression inhibits the growth of breast cancer by upregulating TGF-ß1 and downregulating PHGDH.

Upregulation of lncRNA PlncRNA-1 indicates the poor prognosis and promotes glioma progression by activation of Notch signal pathway.

Prostate cancer-up-regulated long noncoding RNA 1(PlncRNA-1) has been demonstrated to be increased in several cancers, which plays an oncogenic role in the development of cancer. However, the exact functions and molecular mechanism of PlncRNA-1 in the tumorigenesis of glioma has not been studied. In present work, we firstly identified that PlncRNA-1 expression levels were prominently augmented in glioma patient tissues and glioma cell lines compared with adjacent noncancerous tissue and normal cells, respectively. Moreover, Kaplan-Meier survival analysis indicated that glioma patients with high PlncRNA-1 expression had shorter overall survival (OS) and progression-free survival (PFS) than those with low PlncRNA-1 expression. Furthermore, loss-of-function assay showed that PlncRNA-1 knockdown dramatically reduced cell proliferation, colony formation, and promoted apoptosis of glioma cell lines. In addition, overexpression of PlncRNA-1 promoted cell proliferation, stimulated cell colony formation, and inhibited cell apoptosis in NHA cells. Mechanically, our results showed that PlncRNA-1 significantly promoted activation of the Notch signal pathway through regulation of Notch-1, Jag-1, and Hes-1 expression. Collectively, our results implied that lncRNA PlncRNA-1 may exert tumor-promoting role in the development and progression of glioma through modulation of Notch signal pathway, providing a candidate therapeutic target for patients with glioma.

Long non-coding RNA PlncRNA-1 regulates cell proliferation, apoptosis, and autophagy in septic acute kidney injury by regulating BCL2.

This study aimed to elucidate the potential role of long non-coding RNA PlncRNA-1 in the septic acute kidney injury (AKI). The expression of PlncRNA-1 in the serum of patients with septic AKI patient was detected. We then established lipopolysaccharide (LPS)-induced septic AKI model in NRK-52E cells to investigate the effects of the overexpression of PlncRNA-1 on cell proliferation, apoptosis, and autophagy. In addition, the regulatory relationship between PlncRNA-1 and B-cell lymphoma 2 (BCL2) was explored to further elucidate the regulatory mechanism of PlncRNA-1 in septic AKI. PlncRNA-1 is downregulated in the serum of patients with septic AKI and in LPS-induced septic AKI cells. The overexpression of PlncRNA-1 considerably increases proliferation and inhibits apoptosis and autophagy of LPS-induced septic AKI cells. In addition, PlncRNA-1 can promote BCL2 expression, and the overexpression of BCL2 enhances proliferation and inhibits apoptosis and autophagy of LPS-induced septic AKI cells. Our findings reveal that the overexpression of PlncRNA-1 may promote cell proliferation and inhibit apoptosis and autophagy in septic AKI by regulating BCL2 expression. PlncRNA-1 may serve as a potential biomarker or target for the diagnosis and treatment of septic AKI.

Upregulation of long non-coding RNA PlncRNA-1 promotes proliferation and induces epithelial-mesenchymal transition in prostate cancer.

OBJECTIVE: To confirm that PlncRNA-1 regulates the cell cycle in prostate cancer cells and induces epithelial-mesenchymal transition (EMT) in prostate cancer through the TGF-ß1 pathway. RESULTS: PlncRNA-1 and TGF-ß1 expression levels were significantly higher in prostate cancer tissues than in normal prostate tissues (P < 0.05) and were significantly positively correlated. TGF-ß1, N-cadherin and Cyclin-D1 were downregulated and E-Cadherin was upregulated in LNCAP cells after silencing of PlncRNA-1, as determined by real-time PCR and Western blot. TGF-ß1, N-cadherin and Cyclin-D1 were upregulated and E-cadherin was downregulated in C4-2 cells, as determined by real-time PCR and Western blot. Overexpression of PlncRNA-1 in C4-2 cells was observed when TGF-ß1 inhibitor LY2109761 was added. Western blot analysis showed that compared with their expression when TGF-ß1 inhibitor LY2109761 was not added, N-Cadherin and CyclinD1 expression decreased and E-Cadherin expression increased. Transwell results showed that the invasive ability of C4-2 cells was enhanced after overexpression of PlncRNA-1, and the invasion ability was decreased after addition of TGF-ß1 inhibitor LY2109761. The cell cycle was blocked by overexpression of PlncRNA-1 in C4-2 and by the addition of TGF-ß1 inhibitor LY2109761, as determined by flow cytometry. In vitro experiments showed that PlncRNA-1 can regulate the growth of prostate cancer cells and EMT through the TGF-ß1 pathway. In vivo experiments also confirmed the above results. Tumor growth was significantly blocked by overexpressing PlncRNA-1 in C4-2 cells and by the TGF-ß1 inhibitor LY2109761 in animal experiments. MATERIALS AND METHODS: The expression levels of PlncRNA-1 and TGF-ß1 were analyzed in 19 prostate cancer tissue samples and in adjacent normal tissue samples, 4 Pca cell lines, including LNCaP, C4-2,DU145, and PC3, and 1 normal prostate epithelial cell line RWPE-1. LNCAP cells were divided into the LNCAP control group and the LNCAP-PlncRNA-1-siRNA group. Cells from the prostate cancer cell line C4-2 were divided into the C4-2 control group and the C4-2-PlncRNA-1 experimental group. Changes in TGF-ß1, E-cadherin and N-cadherin were detected by qPCR and Western Blot assay after silencing and overexpression of PlncRNA-1. The cell cycle, cell invasion, and levels of Cyclin-D1, E-Cadherin, and N-Cadherin were observed after adding TGF-ß1 inhibitor LY2109761 in the C4-2-PlncRNA-1 group. The effects of TGF-ß1 inhibitor LY2109761 on the tumorigenicity of C4-2 cells after overexpression of PlncRNA-1 was investigated in vivo. CONCLUSIONS: PlncRNA-1 is an oncogene that regulates the cell cycle, cyclin-D1 and EMT in prostate cancer cells through the TGF-ß1 pathway.

Aberrant expression of PlncRNA-1 and TUG1: potential biomarkers for gastric cancer diagnosis and clinically monitoring cancer progression.

AIM: To evaluate PlncRNA-1, TUG1 and FAM83H-AS1 gene expression and their possible role as a biomarker in gastric cancer (GC) progression. PATIENTS & METHODS: Long noncoding RNA expressions and clinicopathological characteristics were assessed in 70 paired GC tissues. Furthermore, corresponding data from 318 GC patients were downloaded from The Cancer Genome Atlas database. RESULTS: Expression of PlncRNA-1 and TUG1 were significantly upregulated in GC tumoral tissues, and significantly correlated with clinicopathological characters. However, FAM83H-AS1 showed no consistently differential expression. The expression of these three long noncoding RNAs was significantly higher in The Cancer Genome Atlas tumoral tissues. CONCLUSION: In conclusion, PlncRNA-1 and TUG1 genes may play a critical role in GC progression and may serve as potential diagnostic biomarkers in GC patients.

A feed-forward regulatory loop between androgen receptor and PlncRNA-1 promotes prostate cancer progression.

We previously reported that PlncRNA-1, a long non-coding RNA that is up-regulated in prostate cancer (PCa), affects the proliferation and apoptosis of PCa cells. However, the molecular mechanisms underlying these effects remain largely unknown. In this study, we demonstrated that long non-coding RNA PlncRNA-1, whose expression is promoted by Androgen Receptor (AR), protects AR from microRNA-mediated suppression in PCa cells. PlncRNA-1 knockdown resulted in the up-regulation of a series of AR-targeting microRNAs, among which miR-34c and miR-297 were found to regulate both AR and PlncRNA-1 expression at the post-transcriptional level. Functional analysis revealed that miR-34c and miR-297 overexpression down-regulated AR expression and inhibited the expression of downstream AR targets and that PlncRNA-1 overexpression rescued these effects. The association of PlncRNA-1 with tumor progression was also evaluated in mouse xenograft models, PCa tissues (16 paired samples), and blood samples (35 biopsy-negative and 37 biopsy-positive). Together, the data generated in this study indicate that PlncRNA-1 sponges AR-targeting microRNAs to protect AR from microRNA-mediated down-regulation and that these events form a regulatory feed-forward loop in the development of PCa. These findings suggest that PlncRNA-1 might potentially serve as a novel biomarker in PCa and that PlncRNA-1 might warrant further investigation to determine its potential role as a promising therapeutic target in PCa.

PlncRNA-1 induces apoptosis through the Her-2 pathway in prostate cancer cells / 亚洲男科学杂志(英文版)

To determine whether PlncRNA-1 induces apoptosis in prostate cancer cells through the Her-2 pathway. The expression of PlncRNA-1, Her-2, and related cyclin proteins in 23 cases of prostate cancer and adjacent normal tissues was analyzed and compared. LNCaP cells were divided into a control group and an LNCaP-PlncRNA-1-siRNA experimental group. Normal prostate RWPE-1 cells were divided into an RWPE-1 control group and an RWPE-1-PlncRNA-1 experimental group. After PlncRNA-1 silencing and overexpression, changes in Her-2 and cyclinD1 expression levels were detected both in vivo and in vitro. In prostate cancer tissues, Her-2 and PlncRNA-1 were highly expressed and significantly correlated. In LNCaP cells, the expression of Her-2 and cyclinD1 decreased following the downregulation of PlncRNA-1 as assessed by real-time PCR and Western blotting. In RWPE-1 cells, the expression of Her-2 and cyclinD1 increased following PlncRNA-1 overexpression. Flow cytometry revealed that the proportion of LNCaP cells in G2/M phase was significantly increased after PlncRNA-1 silencing and that the proportion of RWPE-1 cells in G2/M phase was significantly decreased after PlncRNA-1 overexpression. Furthermore, animal experiments validated these results. In conclusion, in prostate cancer, PlncRNA-1 regulates the cell cycle and cyclinD1 levels and can also regulate proliferation and apoptosis in prostate cancer cells through the Her-2 pathway.