miR‐181c protects CsA‐induced renal damage and fibrosis through inhibiting <scp>EMT</scp>

Sun, Wenjuan; Min, Binying; Du, Dongping; Feng, Yunjiang; Meng, Jian; Wang, Wen; Zhao, Jie; Tan, Xiao; Li, Zhan‐Ting; Sun, Jin

doi:10.1002/1873-3468.12872

Cited by 15 publications

(14 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EMT has been verified to be inhibited by miR-181b (40). Sun et al (35) reported that miR-181c inhibited EMT, thereby protecting cyclosporine A-induced renal damage and fibrosis. Chen et al (4) revealed that the PI3K/Akt signaling pathway serves as a positive regulatory component in the transforming growth factor-␤1-induced EMT of A549 cells.…”

Section: Discussionmentioning

confidence: 99%

Tumor-suppressive effects of microRNA-181d-5p on non-small-cell lung cancer through the CDKN3-mediated Akt signaling pathway in vivo and in vitro

Gao

Zheng

Wang

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

The involvement of several microRNAs (miRs) in the initiation and development of tumors through the suppression of the target gene expression has been highlighted. The aberrant expression of miR-181d-5p and cyclin-dependent kinase inhibitor 3 (CDKN3) in non-small-cell lung cancer (NSCLC) was then screened by microarray analysis. In the present study, we performed a series of in vivo and in vitro experiments for the purpose of investigating their roles in NSCLC and the underlying mechanism. There was a high expression of CDKN3, whereas miR-181d-5p was downregulated in NSCLC. Quantitative RT-PCR, Western blot analysis, and dual-luciferase reporter gene assay further identified that CDKN3 could be negatively regulated by miR-181d-5p. Moreover, the upregulation of miR-181d-5p or silencing of CDKN3 could inactivate the Akt signaling pathway. A549 with the lowest miR-181d-5p and H1975 with the highest CDKN3 among the five NSCLC cell lines (H1299, A549, H1975, NCI-H157, and GLC-82) were adopted for in vitro experiments, in which expression of miR-181d-5p and CDKN3 was altered by transfection of miR-181d-5p mimic/inhibitor or siRNA-targeting CDKN3. Afterwards, cell proliferation, apoptosis, invasion, migration, and angiogenesis, as well as epithelial-mesenchymal transition (EMT), were evaluated, and tumorigenicity was assessed. In addition, an elevation in miR-181d-5p or depletion in CDKN3 led to significant reductions in proliferation, invasion, migration, angiogenesis, EMT, and tumorigenicity of NSCLC cells, coupling with increased cell apoptosis. In conclusion, this study highlights the tumor-suppressive effects of miR-181d-5p on NSCLC via Akt signaling pathway inactivation by suppressing CDKN3, thus providing a promising therapeutic strategy for the treatment of NSCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

Tumor-suppressive effects of microRNA-181d-5p on non-small-cell lung cancer through the CDKN3-mediated Akt signaling pathway in vivo and in vitro

Gao

Zheng

Wang

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Serum albumin, uric acid, serum urea nitrogen and serum creatinine can be used as parameters to evaluate CKD progression (Li et al 2014 ). Up-regulating miR-181c also protects kidneys from CsA-induced renal injury and fibrosis through the suppression of the epithelial-mesenchymal transition (EMT) (Sun et al 2017 ). Consistent with those findings, our study found that miR-181a inhibited both the GS and RTE injury in CKD, which was supported by an apparent decrease in the cell apoptosis rate and the levels of ROS, MDA, IL-1β, IL-6, and TNF-α in the miR-181a mimic group.…”

Section: Discussionmentioning

confidence: 99%

Over-expressed microRNA-181a reduces glomerular sclerosis and renal tubular epithelial injury in rats with chronic kidney disease via down-regulation of the TLR/NF-κB pathway by binding to CRY1

Liu

Pang

Shang

et al. 2018

Mol Med

View full text Add to dashboard Cite

BackgroundMicroRNAs (miRNAs) contribute to the progression of chronic kidney disease (CKD) by regulating renal homeostasis. This study explored the effects of miR-181a on CKD through the Toll-like receptor (TLR)/nuclear factor-kappa B (NF-κB) pathway by binding to CRY1.MethodsSeventy male rats were selected and assigned into specific groups: miR-181a mimic, miR-181a inhibitor, and siRNA against CRY1, with each group undergoing different treatments to investigate many different outcomes. First, 24-h urinary protein was measured. ELISA was used to determine the serum levels of SOD, ROS, MDA, IL-1β, IL-6, and TNF-α. Biochemical tests for renal function were performed to measure albumin, uric acid, and urea in urine and urea nitrogen and creatinine in serum. The glomerulosclerosis index (GSI) and renal tubular epithelial (RTE) cell apoptosis were detected using PASM staining and TUNEL staining, respectively. Finally, RT-qPCR and western blot were done to determine miR-181a, CRY1, TLR2, TLR4, and NF-κB expression.ResultsCRY1 is the target gene of miR-181a, according to a target prediction program and luciferase assay. Rats diagnosed with CKD presented increases in 24-h urinary protein; GSI; RTE cell apoptosis rate; serum ROS, MDA, IL-1β, IL-6, and TNF-α; and CRY1, TLR2, TLR4, and NF-κB expression, as well as decreases in SOD level and miR-181a expression. Following transfection with either the miR-181a mimic or si-CRY1, 24-h urinary protein, renal damage, GSI, and cell apoptosis rate were all decreased. In addition, the overexpression of miR-181a or inhibition of CRY1 alleviated the degree of kidney injury through suppression of the TLR/NF-κB pathway.ConclusionmiR-181a alleviates both GS and RTE injury in CKD via the down-regulation of the CRY1 gene and the TLR/NF-κB pathway.

show abstract

“…It plays an important role in embryonic development, tumor metastasis, and tissue fibrosis (Carew et al, 2012;Allison, 2015). More and more evidences showed that EMT is a typical feature of renal fibrosis, and EMT of tubular epithelial cells contributes significantly to the occurrence, development, and pathological processes of kidney fibrosis (Sharma, 2014;Sun et al, 2017). Transforming growth factor-β1 (TGF-β1) is a typical pro-fibrotic cytokine involved in the process of EMT (Zhao et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-140-5p Mediates Renal Fibrosis Through TGF-β1/Smad Signaling Pathway by Directly Targeting TGFBR1

et al. 2020

View full text Add to dashboard Cite

Renal tubulointerstitial fibrosis is usually the final outcome of various end-stage renal diseases. Recent studies have reported that microRNAs (miRNAs) play an important role in renal fibrosis. However, the biological function of microRNAs in renal fibrosis is complicated and remains unclear. In this study, our results show that miR-140-5p expression is significantly down-regulated in mice with unilateral ureteral obstruction and human proximal tubule epithelial cells (HK2) treated with TGF-β1. The knockdown of miR-140-5p upregulates the expression levels of collagen I, collagen IV, and α-SMA, decreases E-cadherin expression, and increases Smad-2/3 phosphorylation. In contrast, the overexpression of miR-140-5p decreases the expression levels of collagen I, collagen IV, and α-SMA, enhances E-cadherin expression, and inhibits the phosphorylation of Smad-2/3 in HK2 cells treated with TGF-β1. The dual-luciferase reporter assay revealed that TGFBR1 is a direct target gene of miR-140-5p. The enforced expression of miR-140-5p significantly inhibited the expression of TGFBR1 in HK2 cells. Furthermore, the knockdown of TGFBR1 has a similar effect of miR-140-5p overexpression on blocking the TGF-β1/smad signal pathway activation. In contrast, the overexpression of TGFBR1 reverses the effect of miR-140-5p inhibition on the activation of the TGF-β1/smad signal pathway. This study demonstrates that miR-140-5p regulates the TGF-β1/smad signaling pathway by suppressing the expression of TGFBR1. Therefore, miR-140-5p may have a therapeutic potential for preventing fibrotic kidney diseases through inhibiting the TGF-β1/Smad signaling pathway by directly targeting TGFBR1.

show abstract

miR‐181c protects CsA‐induced renal damage and fibrosis through inhibiting EMT

Cited by 15 publications

References 35 publications

Tumor-suppressive effects of microRNA-181d-5p on non-small-cell lung cancer through the CDKN3-mediated Akt signaling pathway in vivo and in vitro

Tumor-suppressive effects of microRNA-181d-5p on non-small-cell lung cancer through the CDKN3-mediated Akt signaling pathway in vivo and in vitro

Over-expressed microRNA-181a reduces glomerular sclerosis and renal tubular epithelial injury in rats with chronic kidney disease via down-regulation of the TLR/NF-κB pathway by binding to CRY1

MicroRNA-140-5p Mediates Renal Fibrosis Through TGF-β1/Smad Signaling Pathway by Directly Targeting TGFBR1

Contact Info

Product

Resources

About