High glucose increases miR‐214 to power a feedback loop involving PTEN and the Akt/mTORC1 signaling axis

Maity, Soumya; Das, Falguni; Ghosh‐Choudhury, Nandini; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh

doi:10.1002/1873-3468.13505

Cited by 14 publications

(10 citation statements)

References 52 publications

(100 reference statements)

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“…Many studies on kidney-related diseases, such as diabetic nephropathy and acute kidney injury models, have revealed the role of miR-214 [9,35,36], but the mechanism of miR-214 in renal interstitial fibrosis has rarely been investigated. According to our research, we confirmed that miR-214-3p levels were upregulated, PTEN expression was decreased in UUO mice, and this effect was related to renal interstitial 11 Oxidative Medicine and Cellular Longevity fibrosis (Figure 1), which was consistent with existing reports [20,37].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of miR-214 Alleviates Renal Interstitial Fibrosis by Targeting the Regulation of the PTEN/PI3K/AKT Signalling Pathway

Hou

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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The microRNA-214 (miR-214) precursor is formed by the DNM3 gene on human chromosome 1q24.3, which is encoded and transcribed in the nucleus and processed into mature miR-214 in the cytoplasm. Association of miR-214 with the interstitial fibrosis of the kidney has been reported in existing research. Renal interstitial fibrosis is considered necessary during the process of various renal injuries in chronic kidney disease (CKD). One of the important mechanisms is the TGF- (transforming growth factor-) β1-stimulated epithelial interstitial transformation (EMT). The specific mechanisms of miR-214-3p in renal interstitial fibrosis and whether it participates in EMT are worthy of further investigation. In this paper, we first demonstrated modulation of the downstream PI3K/AKT axis by miR-214-3p through targeting phosphatase and tension protein homologues (PTEN), indicating the miRNA’s participation in unilateral ureteral obstruction (UUO) nephropathy and TGF-β1-induced EMT. We overexpressed or silenced miR-214-3p and PTEN for probing into the correlation of miR-214-3p with PTEN and the downstream PI3K/AKT signalling pathways. According to the results of the study, miR-214-3p overexpression silenced PTEN, activated the PI3K/AKT signalling pathway, and exacerbated EMT induced by TGF-β1, while miR-214-3p knockdown had the opposite effect. In miR-214-3p knockdown mice, the expression of PTEN was increased, the PI3K/AKT signalling pathway was inhibited, and fibrosis was alleviated. In conclusion, miR-214-3p regulates the EMT of renal tubular cells induced by TGF-β1 by targeting PTEN and regulating the PI3K/AKT signalling pathway. Furthermore, miR-214-3p knockdown can reduce renal interstitial fibrosis through the PTEN/PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 99%

Knockdown of miR-214 Alleviates Renal Interstitial Fibrosis by Targeting the Regulation of the PTEN/PI3K/AKT Signalling Pathway

Hou

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Analysis of variance followed by Tukey's multiple comparison test was used. A p value of < 0.05 was considered as significant (97).…”

Section: Discussionmentioning

confidence: 99%

TGFβ acts through PDGFRβ to activate mTORC1 via the Akt/PRAS40 axis and causes glomerular mesangial cell hypertrophy and matrix protein expression

Maity

Das

Kasinath

et al. 2020

Journal of Biological Chemistry

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Interaction of TGFβ-induced canonical signaling with the noncanonical kinase cascades regulates glomerular hypertrophy and matrix protein deposition, which are early features of glomerulosclerosis. However, the specific target downstream of TGFβ receptor involved in the noncanonical signaling is unknown. Here, we show that TGFβ increased the catalytic loop phosphorylation of platelet-derived growth factor receptor beta (PDGFRβ), a receptor tyrosine kinase expressed abundantly in glomerular mesangial cells. TGFβ increased phosphorylation of the PI 3 kinase-interacting Tyr-751 residue of PDGFRβ, thus activating Akt. Inhibition of PDGFRβ using a pharmacological inhibitor and siRNAs blocked TGFβ-stimulated phosphorylation of PRAS40, an intrinsic inhibitory component of mTORC1, and prevented activation of mTORC1 in the absence of any effect on Smad 2/3 phosphorylation. Expression of constitutively active Myr-Akt reversed the siPDGFRβ-mediated inhibition of mTORC1 activity; however, co-expression of phospho-deficient mutant of PRAS40 inhibited the effect of Myr-Akt, suggesting a definitive role of PRAS40 phosphorylation in mTORC1 activation downstream of PDGFRβ in mesangial cells. Additionally, we demonstrate that PDGFRβ-initiated phosphorylation of PRAS40 is required for TGFβ-induced mesangial cell hypertrophy and, fibronectin and collagen I (α2) production. Increased activating phosphorylation of PDGFRβ is also associated with enhanced TGFβ expression and mTORC1 activation in the kidney cortex and glomeruli of diabetic mice and rat, respectively. Thus, pursuing the TGFβ noncanonical signaling, we identified how TGFβ receptor I achieves mTORC1 activation through PDGFRβ-mediated Akt/PRAS40 phosphorylation to spur mesangial cell hypertrophy and matrix protein accumulation. These findings provide support for targeting PDGFRβ in TGFβ-driven renal fibrosis.

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“…miR-214 functions as a pro-metastatic factor in malignant tumors ( 42 ), and plays a critical role in the migration and invasion of cancer cells ( 43 – 45 ). The present study identified a potential link between miR-214 and CADM1 in the coordination of metastasis in melanoma.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑214 promotes the EMT process in melanoma by downregulating CADM1 expression

Wang

Wen

et al. 2020

Mol Med Rep

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Melanoma is a malignant skin cancer type associated with a high mortality rate, but its treatment is currently not ideal. Both microrna (mir)-214 and cell adhesion molecule 1 (cadM1) are differentially expressed in melanoma, but their role in this cancer type remains unknown. Therefore, the aim of the present study was to investigate the role of cadM1 and mir-214 in melanoma to identify novel targets for its treatment. The expression levels of cadM1 and mir-214 in cells were detected by reverse transcription-quantitative Pcr (rT-qPcr). Moreover, cell viability, migration and invasion were measured by MTT, wound healing and Transwell assays, respectively. in addition, the relative expression levels of epithelial-mesenchymal transition (eMT)-related proteins in cells were detected by rT-qPcr and western blotting. it was found that the expression of cadM1 was inhibited in melanoma cells, while mir-214 expression was increased during melanoma tumorigenesis. Furthermore, mir-214 mimics promoted the viability, migration and invasion of melanoma cells. it was also demonstrated that the downregulation of cadM1 reversed the inhibitory effect of the mir-214 inhibitor in melanoma. Moreover, overexpression of cadM1 inhibited the eMT process in melanoma, while the mir-214 inhibitor suppressed the eMT process. The results also indicated that mir-214 promoted the eMT process by downregulating cadM1, which may represent a novel mechanism for the progression of melanoma.

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High glucose increases miR‐214 to power a feedback loop involving PTEN and the Akt/mTORC1 signaling axis

Cited by 14 publications

References 52 publications

Knockdown of miR-214 Alleviates Renal Interstitial Fibrosis by Targeting the Regulation of the PTEN/PI3K/AKT Signalling Pathway

Knockdown of miR-214 Alleviates Renal Interstitial Fibrosis by Targeting the Regulation of the PTEN/PI3K/AKT Signalling Pathway

TGFβ acts through PDGFRβ to activate mTORC1 via the Akt/PRAS40 axis and causes glomerular mesangial cell hypertrophy and matrix protein expression

MicroRNA‑214 promotes the EMT process in melanoma by downregulating CADM1 expression

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