Dataset Information

SP1-mediated lncRNA PVT1 modulates the proliferation and apoptosis of lens epithelial cells in diabetic cataract via miR-214-3p/MMP2 axis.

ABSTRACT: Emerging evidence illustrates the critical roles of long non-coding RNAs (lncRNAs) in the diabetes. However, the deepgoing regulation of lncRNA PVT1 in the diabetic cataract (DC) is still unclear. Here, present research investigates the pathologic roles and underlying mechanism by which lncRNA PVT1 regulates the DC pathogenesis. Human lens epithelial (HLE) B-3 cells were induced by the high glucose (HG) to simulate the DC microenvironment models. Results revealed that lncRNA PVT1 expression was up-regulated in the HG-induced HLE B-3 cells as compared to the normal glucose group. Transcription factor SP1 could bind with the promoter region of PVT1 and activate its transcription. Functionally, PVT1 knock-down could repress the proliferation and promote the apoptosis of HLE B-3 cells. Mechanistically, PVT1 acted as the 'miRNA sponge' to target miR-214-3p/MMP2 axis. This finding revealed a novel insight of lncRNA PVT1 for the DC pathogenesis, providing an inspiration for the DC mechanism.

SUBMITTER: Yang J

PROVIDER: S-EPMC6933388 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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SP1-mediated lncRNA PVT1 modulates the proliferation and apoptosis of lens epithelial cells in diabetic cataract via miR-214-3p/MMP2 axis.

Yang Jun J Zhao Shaozhen S Tian Fang F

Journal of cellular and molecular medicine 20191121 1

Emerging evidence illustrates the critical roles of long non-coding RNAs (lncRNAs) in the diabetes. However, the deepgoing regulation of lncRNA PVT1 in the diabetic cataract (DC) is still unclear. Here, present research investigates the pathologic roles and underlying mechanism by which lncRNA PVT1 regulates the DC pathogenesis. Human lens epithelial (HLE) B-3 cells were induced by the high glucose (HG) to simulate the DC microenvironment models. Results revealed that lncRNA PVT1 expression was ...[more]

PMID: 31755246

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Project description:BackgroundTreating advanced colon cancer remains challenging in clinical settings because of the development of drug resistance and distant metastasis. Mechanisms underlying the metastasis of colon cancer are complex and unclear.MethodsComputational analysis was performed to determine genes associated with the exosomal long noncoding (lncRNA) plasmacytoma variant translocation 1 (PVT1)/vascular endothelial growth factor A (VEGFA) axis in patients with colon cancer. The biological importance of the exosomal lncRNA PVT1/VEGFA axis was examined in vitro by using HCT116 and LoVo cell lines and in vivo by using a patient-derived xenograft (PDX) mouse model through knockdown (by silencing of PVT1) and overexpression (by adding serum exosomes isolated from patients with distant metastasis (M-exo)).ResultsThe in silico analysis demonstrated that PVT1 overexpression was associated with poor prognosis and increased expression of metastatic markers such as VEGFA and epidermal growth factor receptor (EGFR). This finding was further validated in a small cohort of patients with colon cancer in whom increased PVT1 expression was correlated with colon cancer incidence, disease recurrence, and distant metastasis. M-exo were enriched with PVT1 and VEGFA, and both migratory and invasive abilities of colon cancer cell lines increased when they were cocultured with M-exo. The metastasis-promoting effect was accompanied by increased expression of Twist1, vimentin, and MMP2. M-exo promoted metastasis in PDX mice. In vitro silencing of PVT1 reduced colon tumorigenic properties including migratory, invasive, colony forming, and tumorsphere generation abilities. Further analysis revealed that PVT1, VEGFA, and EGFR interact with and are regulated by miR-152-3p. Increased miR-152-3p expression reduced tumorigenesis, where increased tumorigenesis was observed when miR-152-3p expression was downregulated.ConclusionExosomal PVT1 promotes colon cancer metastasis through its association with EGFR and VEGFA expression. miR-152-3p targets both PVT1 and VEGFA, and this regulatory pathway can be explored for drug development and as a prognostic biomarker.

Project description:Long noncoding RNA (lncRNAs) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported in diabetic nephropathy (DN) about its effect on podocyte function and cell heat shock induced by hyperglycemia. However, the biological mechanism of MALAT1 regulating DN fibrosis needs further study. In this study, SD rats were administrated with streptozotocin (STZ) to establish a diabetes model. In vitro, human renal tubular epithelial cells (HK-2 and 293T) were treated with high glucose (HG). Here, we found that MALAT1 was upregulated in renal tissues of diabetic rats and HG-treated cells, and HG treatment promoted cell proliferation and invasion. MALAT1 overexpression aggravated protein levels of collagen I (col I), collagen IV (col IV), fibronectin (FN), and laminin (LN) in HK-2 cells, while MALAT1 knockdown exerted the opposite effect. Moreover, the luciferase reporter gene and pull-down assays demonstrated that MALAT1 interacted with miR-2355-3p. The miR-2355-3p level was downregulated in diabetic rats and HG-treated cells, and MALAT1 overexpression inhibited the miR-2355-3p level. Bioinformatics prediction and luciferase reporter gene assay revealed that interleukin 6 signal transducer (IL6ST) was a target of miR-2355-3p. In addition, miR-2355-3p overexpression attenuated fibrosis-related gene levels in HG-treated cells by inhibiting IL6ST expression and inactivating the recombinant signal transducer and activator of the transcription 3 (STAT3) signaling pathway. Knockdown of miR-2355-3p reversed the inhibitory effect of MALAT1 knockdown on IL6ST, col I, col IV, FN, and LN protein levels in HG-induced cells. Overexpression of MALAT1 aggravated cell damage in HG-induced cells via the miR-2355-3p/IL6ST/STAT3 signaling pathway. Finally, enhanced renal fibrosis and kidney tissue damage were observed in diabetic rats. In conclusion, MALAT1 overexpression may enhance renal fibrosis in diabetic rats and cell damage in HG-induced HK-2 cells via the miR-2355-3p/IL6ST axis, which provides a new perspective of DN treatment.

Dataset Information

SP1-mediated lncRNA PVT1 modulates the proliferation and apoptosis of lens epithelial cells in diabetic cataract via miR-214-3p/MMP2 axis.

Publications

SP1-mediated lncRNA PVT1 modulates the proliferation and apoptosis of lens epithelial cells in diabetic cataract via miR-214-3p/MMP2 axis.

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