Long Non-Coding RNA MALAT1 Mediates Transforming Growth Factor Beta1-Induced Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells

Yang, Shuai; Yao, Haipei; Li, Min; Li, Hui; Wang, Fang

doi:10.1371/journal.pone.0152687

Cited by 56 publications

(62 citation statements)

References 30 publications

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“…1B, 1C), indicating that the cells underwent EndMT. Previous studies have shown that MALAT1 is highly expressed in endothelial cells [38], and it is induced by TGF-β in cancer and epithelial cells, mediating TGF-β1-induced EMT [32, 39]. In this study, we found thatTGF-β1 strongly induced MALAT1 mRNA expression in EPCs (Fig.…”

Section: Resultssupporting

confidence: 72%

“…Extensive studies have indicated that MALAT1 plays an oncogenic role in various cancers via multiple mechanisms, including triggering EMT in tumor cells and promoting tumor metastasis [28, 31]. Importantly, MALAT1 has been found to be induced by TGF-β1 and mediate TGF-β1-triggered EMT in retinal pigment epithelial cells [32]. However, whether MALAT1 contributes to EndMT induced by TGF-β1 is not clear.…”

Section: Introductionmentioning

confidence: 99%

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MALAT1 Modulates TGF-β1-Induced Endothelial-to-Mesenchymal Transition through Downregulation of miR-145

Yin¹,

Zhang²,

Tang³

et al. 2017

Cell Physiol Biochem

114

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Background/Aims: Endothelial-to-mesenchymal transition (EndMT) plays significant roles under various pathological conditions including cardiovascular diseases, fibrosis, and cancer. EndMT of endothelial progenitor cells (EPCs) contributes to neointimal hyperplasia following cell therapy Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that promotes metastasis and cancer. MicroRNA-145 (miR-145) is a tumor suppressor that has been reported to inhibit SMAD3-mediated epithelial-to-mesenchymal transition (EMT) of cancer cells. In the present study, we investigated the role of MALAT1 and miR-145 in EndMT of human circulating EPCs induced by transforming growth factor beta1 (TGF-β1). Methods: Human circulating EPCs were isolated and characterized by fluorescence-activated cell sorting (FACS). Expression levels of EndMT markers were assessed by qRT-PCR and western blotting. Alpha-smooth muscle actin (α-SMA) expression was measured by cell immunofluorescence staining. The regulatory relationship between MALAT1 and miR-145 and its target genes, TGFBR2 (TGFβ receptortype II) and SMAD3 (mothers against decapentaplegic homolog 3) was analyzed using the luciferase reporter assay. Results: We found that EndMT of EPCs induced by TGF-β1 is accompanied by increased MALAT1 expression and decreased miR-145 expression, and MALAT1 and miR-145 directly bind and reciprocally repress each other in these cells. Dual-Luciferase Reporter assay indicated that miR-145 inhibits TGF-β1-induced EndMT by directly targeting TGFBR2 and SMAD3. Conclusions: MALAT1 modulates TGF-β1-induced EndMT of EPCs through regulation of TGFBR2 and SMAD3 via miR-145. Thus, the MALAT1-miR-145-TGFBR2/SMAD3 signaling pathway plays a key role in TGF-β1-induced EndMT.

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Section: Resultssupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

MALAT1 Modulates TGF-β1-Induced Endothelial-to-Mesenchymal Transition through Downregulation of miR-145

Yin¹,

Zhang²,

Tang³

et al. 2017

Cell Physiol Biochem

114

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“…It is reported that autophagy that induced by pharmacology in vivo could increase the number of living cells after traumatic injury, implying that autophagy play a cytoprotective role in RGCs and the regulation of autophagy might provide a novel therapeutic strategy to mitigate retinal nerve diseases [35]. LncRNA-MALAT1 can be induced by TGF-β1, and LncRNA-MALAT1 silencing affects TGF-β1 function and may indirectly regulate neuronal apoptosis by upregulating Bcl-2 expression [36, 37]. Jin Yao et al also confirmed the decrease in IPL and GCL cells after LncRNA-MALAT1 knockdown, indicating that LncRNA-MALAT1 knockdown affects the survival of RGCs; moreover, LncRNA-MALAT1 expression affects RGC functions, such as RGC viability, proliferation and apoptosis, suggesting that LncRNA-MALAT1 plays an important role in RGC survival and morphology [38].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma

You

et al. 2017

Cell Physiol Biochem

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Background/Aims: The aim of the present study is to investigate the effect of long non-coding RNA-MALAT1 (LncRNA-MALAT1) on retinal ganglion cell (RGC) apoptosis mediated by the PI3K/Akt signaling pathway in rats with glaucoma. Methods: RGCs were isolated and cultured, and monoclonal antibodies (anti-rat Thy-1, Brn3a and RBPMS) were examined by immunocytochemistry. An overexpression vector MALAT1-RNA activation (RNAa), gene knockout vector MALAT1-RNA interference (RNAi), and control vector MALAT1-negative control (NC) were constructed. A chronic high intraocular pressure (IOP) rat model of glaucoma was established by episcleral vein cauterization. The RGCs were divided into the RGC control, RGC pressure, RGC pressure + MALAT1-NC, RGC pressure + MALAT1-RNAi and RGC pressure + MALAT1-RNAa groups. Sixty Sprague-Dawley (SD) rats were randomly divided into the normal, high IOP, high IOP + MALAT1-NC, high IOP + MALAT1-RNAa and high IOP + MALAT1-RNAi groups. qRT-PCR and western blotting were used to detect the expression levels of LncRNA-MALAT1 and PI3K/Akt. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect RGC apoptosis. Results: Immunocytochemistry revealed that the cultured RGCs reached 90% purity. Compared with the RGC pressure + MALAT1-NC group, the RGC pressure + MALAT1-RNAa group exhibited elevated expression levels of MALAT1, lower total protein levels of PI3K and Akt and decreased RGC apoptosis, while these expression levels were reversed in the RGC pressure + MALAT1-RNAi group. RGC numbers and PI3K/Akt expression levels in the high IOP model groups were lower than those in the normal group. In the high IOP + MALAT1-RNAa group, the mRNA and protein expression levels of PI3K/Akt were reduced but higher than those in the other three high IOP model groups. Additionally, RGC numbers in the high IOP + MALAT1-RNAa group were lower than those in the normal group but higher than those in the other three high IOP model groups. Conclusion: Our study provides evidence that LncRNA-MALAT1 could inhibit RGC apoptosis in glaucoma through activation of the PI3K/Akt signaling pathway.

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“…10 However, it focused on late AMD, and most attention was paid to neovascularization, which was quite different during early AMD. Several previous studies reported that lncRNAs were associated with epithelial-mesenchymal transition of RPE cells, 26 maintenance of retinal architecture, 27 and regulation of microvascular dysfunction in DR. 28 In this study, we conducted an overall review of the expression patterns of lncRNAs in early AMD. It was found that a total of 64 lncRNAs were dysregulated in early AMD.…”

mentioning

confidence: 98%

Identification of lncRNAs involved in biological regulation in early age-related macular degeneration

Zhu

Xing

et al. 2017

IJN

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Background Age-related macular degeneration (AMD) is one of the most common causes of adult blindness in developed countries. However, the role of long noncoding RNAs (lncRNAs) in the development and progression of early AMD is unclear. Methods We established the lncRNA profile of early AMD by reannotation of microarrays from the gene expression omnibus database. Quantitative real-time polymerase chain reaction was used to determine the expression of selected lncRNAs. Results The expression profiles of 9 cases of AMD and 7 controls were studied. A total of 266 differentially expressed genes (DEGs) were detected (94 upregulated and 172 downregulated). Among all the DEGs, 64 were lncRNAs. Advanced bioinformatics analyses demonstrated that differentially expressed lncRNAs could play significant roles in visual perception, sensory perception of light stimulus, and cognition. The pathway analyses showed that the two most significantly influenced Kyoto Encyclopedia of Genes and Genomes pathways were those of phototransduction and purine metabolism. By the analyses of the key lncRNAs, it was found that RP11-234O6.2 was downregulated in the aging retinal pigment epithelium (RPE) cellular model. Exogenous RP11-234O6.2 treatment led to increased cell viability and improved apoptosis but it did not affect the cell migration ability of aging RPE cells. Conclusion This study indicated that lncRNAs are differentially expressed in early AMD and may produce important regulative effects. An lncRNA, RP11-234O6.2, might be involved in the biological regulation of early AMD and have therapeutic potential.

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Long Non-Coding RNA MALAT1 Mediates Transforming Growth Factor Beta1-Induced Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells

Cited by 56 publications

References 30 publications

MALAT1 Modulates TGF-β1-Induced Endothelial-to-Mesenchymal Transition through Downregulation of miR-145

MALAT1 Modulates TGF-β1-Induced Endothelial-to-Mesenchymal Transition through Downregulation of miR-145

Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma

Identification of lncRNAs involved in biological regulation in early age-related macular degeneration

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