miR-195-5p is critical in REGγ-mediated regulation of wnt/β-catenin pathway in renal cell carcinoma

Chen, Shaojun; Wang, Longsheng; Yao, Xudong; Chen, Hui; Xu, Chun‐Fang; Lu, Tong; Shah, Abdussaboor; Huang, Tingmei; Chen, Geng; Chen, Jiwei; Liu, Tielong; Li, Xiao-Tao; Zheng, Junhua; Li, Lei

doi:10.18632/oncotarget.19256

Cited by 36 publications

(26 citation statements)

References 29 publications

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“…Knockdown of VEGFA induced NRK-52E cell proliferation and inhibited apoptosis triggered by the inhibitors of miR-195-5p. miR-195-5p is involved in the REGγ-regulated Wnt pathway in RCC [25]. miR-195 can induce mouse podocyte apoptosis by activating caspase activity [26].…”

Section: Discussionmentioning

confidence: 99%

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miR-195-5p alleviates acute kidney injury through repression of inflammation and oxidative stress by targeting vascular endothelial growth factor A

Jiang

Zhong

et al. 2020

Aging

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Acute kidney injury (AKI) is a common renal dysfunction. Renal ischemia-reperfusion (I/R) injury contributes to AKI progression. The microRNA miR-195-5p can act as a crucial tumor inhibitor in various cancers. However, the potential biological effects of miR-195-5p on AKI are not well-understood. We found that miR-195-5p levels were decreased in the serum samples of patients with AKI. Next, we determined miR-195-5p expression in the renal tissues of the rats and found that it was downregulated. Renal function was evaluated and confirmed using blood urea nitrogen and serum Cr levels. In parallel, the hypoxia-induced NRK-52E cell model was employed, and miR-195-5p was found to be markedly reduced under hypoxic conditions. Furthermore, miR-195-5p was modulated in NRK-52E cells. miR-195-5p induced NRK-52E cell proliferation and protected NRK-52E cells against hypoxia-triggered apoptosis. In an I/R mouse model, miR-195-5p alleviated renal injury triggered by I/R. In addition, oxidative stress and inflammatory factor concentrations were assessed using ELISA. The results showed that miR-195-5p mimicked attenuated oxidative stress induced by I/R injury and downregulated the protein expression of inflammatory factors. Moreover, we identified that vascular endothelial growth factor A (VEGFA) was a target gene of miR-195-5p, which could negatively regulate VEGFA expression in vitro. Inhibitors of miR-195-5p subsequently contributed to renal injury, which was reversed by VEGFA loss. In conclusion, miR-195-5p may repress AKI by targeting VEGFA.

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Section: Discussionmentioning

confidence: 99%

“…miR-195-5p is involved in the REGγ-regulated Wnt pathway in RCC [ 25 ]. miR-195 can induce mouse podocyte apoptosis by activating caspase activity [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

miR-195-5p alleviates acute kidney injury through repression of inflammation and oxidative stress by targeting vascular endothelial growth factor A

Jiang

Zhong

et al. 2020

Aging

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“…Recently, an increasing body of evidence has revealed that miRNAs serve an important role in cartilage formation and OA development (13,14). miR-195-5p, a member of the miR-15a/b/16/195/497 family, is currently extensively studied in the development of tumors (16–19). However, the role of miR-195-5p in OA is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…miR-195-5p, a member of the miR-15a/b/16/195/497 family, is located on chromosome 17p13.1 (15). In recent years, the role of miR-195-5p in tumors has been extensively studied (16–19). However, the function of miR-195-5p in OA is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑195‑5p inhibitor prevents the development of osteoarthritis by targeting REGγ

et al. 2019

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Osteoarthritis (OA) is a common inflammatory joint disease. MicroRNAs (miRNAs/miRs) have been reported to be involved in the pathogenesis of OA; however, the role of miRNAs in OA remains largely unexplained. The purpose of the present study was to investigate the expression and role of miR-195-5p in OA, and to further explore the mechanism. The expression level of miR-195-5p was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). TargetScan and a luciferase reporter assay were used to reveal the associations between miR-195-5p and REGγ (also known as PSME3). To investigate the role of miR-195-5p in OA, a cell model of OA was established by treating ATDC5 cells with lipopolysaccharide (LPS). Then an MTT assay was conducted to detect cell proliferation ability, and an Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit was used to measure cell apoptosis. In addition, the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were determined using ELISA. Furthermore, gene and protein expression was measured via RT-qPCR and western blot assay, respectively. The results revealed that miR-195-5p was significantly upregulated in the articular cartilage tissues of patients with OA and in LPS stimulated ATDC5 cells. REGγ was a direct target of miR-195-5p. The repressed cell proliferation ability and enhanced cell apoptosis of ATDC5 cells induced by LPS were reversed by miR-195-5p downregulation. Furthermore, LPS stimulation significantly upregulated the levels of IL-1β, IL-6 and TNF-α, while miR-195-5p downregulation markedly reduced the expression of inflammatory factors induced by LPS. The results also revealed that a miR-195-5p inhibitor inhibited the LPS induced repression of the Wnt/β-catenin signaling pathway and activation of nuclear factor (NF)-κB signaling pathway in ATDC5 cells. Notably, the results of the present study also indicated that all of the effects of the miR-195-5p inhibitor on ATDC5 cells were reversed by REGγ silencing. In conclusion, the results indicated that the miR-195-5p inhibitor served a protective role in OA by inhibiting chondrocyte apoptosis and inflammatory responses by regulating the Wnt/β-catenin and NF-κB signaling pathways.

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“…Aberrant expression of miR-195-5p is associated with various types of cancer. For example, miR-195-5p serves as a tumor suppressor in renal cell carcinoma via REGγ-mediated regulation of the wnt/β-catenin pathway ( 23 ). The overexpression of miR-195-5p promotes apoptosis, and reduces cell growth, migration and invasion in oral squamous cell carcinoma via targeting tripartite motif-containing 14 ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

miR‑195‑5p regulates multi‑drug resistance of gastric cancer cells via targeting ZNF139

Nie

Mu²,

Wang³

et al. 2018

Oncol Rep

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Gastric cancer (GC) is one of the most common malignant tumors with a high mortality rate. Reversing the multi-drug resistance (MDR) of GC offers the potential for significant enhancement of the effect of chemotherapy and improvement of prognosis. Aberrant microRNA expression can attribute to the pathogenesis of GC. However, the effects of microRNA (miR)-195-5p on the MDR of GC cells remains to be fully elucidated. In the present study, the effect of miR-195-5p in regulating the MDR of GC cells was investigated. Reverse transcription quantitative-polymerase chain reaction was used to analyze the levels of miR-195-5p in GC cells. Western blot analysis was performed to analyze the protein levels of ZNF139, P-gp, BCL-2 and MRP1. The chemosensitivity of GC cells was determined by MTT. The results showed that the expression of miR-195-5p was decreased in poorly differentiated GC tissues with a higher chemosensitivity. The overexpression of miR-195-5p promoted the chemosensitivity of GC cells. Bioinformatics analysis indicated that Zing finger 139 (ZNF139) was a target of miR-195-5p. miR-195-5p negatively regulated the expression of ZNF139 by binding to its 3′-untranslated region. The silencing of ZNF139 promoted the chemosensitivity of GC cells, and the downregulation of ZNF139 reversed the effect of miR-195-5p inhibitor on the chemosensitivity of GC cells. In conclusion, miR-195-5p regulated the MDR of GC cells via targeting ZNF139.

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miR-195-5p is critical in REGγ-mediated regulation of wnt/β-catenin pathway in renal cell carcinoma

Cited by 36 publications

References 29 publications

miR-195-5p alleviates acute kidney injury through repression of inflammation and oxidative stress by targeting vascular endothelial growth factor A

miR-195-5p alleviates acute kidney injury through repression of inflammation and oxidative stress by targeting vascular endothelial growth factor A

MicroRNA‑195‑5p inhibitor prevents the development of osteoarthritis by targeting REGγ

miR‑195‑5p regulates multi‑drug resistance of gastric cancer cells via targeting ZNF139

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