scholarly journals Role of SIRT2 in Regulation of Stemness of Cancer Stem-Like Cells in Renal Cell Carcinoma

2018 ◽  
Vol 49 (6) ◽  
pp. 2348-2357 ◽  
Author(s):  
Ruojing Wei ◽  
Dalin He ◽  
Xinshi Zhang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cancer Metastasis ◽  
Fluorescent Protein ◽  
Luciferase Reporter ◽  
Tumor Sphere ◽  
Bivariate Correlation ◽  
Induced Apoptosis

Background/Aims: Cancer stem cells (CSCs) contribute to tumorgenesis, invasion and metastasis, and are typically resistant to chemotherapy. Recent reports showed that SIRT2 was upregulated in several cancers. However, whether SIRT2 may be a CSC marker in renal cell carcinoma (RCC) is not clear. Methods: The SIRT2 levels in both RCC samples and the corresponding normal kidney samples (NT) were assessed by RT-qPCR and ELISA. The association between SIRT2 levels and patient survival was examined using Bivariate correlation analysis by Spearman’s Rank Correlation Coefficients. The survival of the patients was analyzed using Kaplan-Meier curve. In vitro, 2 RCC cell lines were co-transduced with a lentivirus expressing both a green fluorescent protein and a luciferase reporter under a cytomegalovirus promoter, and another lentivirus expressing a nuclear red fluorescent protein reporter under the control of a SIRT2 promoter for differentiating SIRT2+ vs SIRT2- RCC cells by flow cytometry. The SIRT2+ vs SIRT2- RCC cells were examined for the potential of forming tumor sphere in a tumor sphere formation assay, resistance to fluorouracil-induced apoptosis by CCK-8 assay, and the frequency of forming tumor in vivo after serial adoptive transplantation by bioluminescence. Results: The levels of SIRT2 were higher in RCC samples than NT. The prognosis of RCC patients with high SIRT2 was worse than that of with low SIRT2. Compared to SIRT2- cells, SIRT2+ cells formed more tumor spheres, appeared to be more resistant towards fluorouracil-induced apoptosis, and generated bigger tumors with higher frequency after serial adoptive transplantation. Conclusion: SIRT2 may be highly expressed in the RCC stem-like cells and regulates cancer metastasis. Selective knockout of SIRT2 or elimination of SIRT2+ cells may improve the therapeutic outcome for patients with RCC.

scholarly journals Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Junjie Cen ◽  
Yanping Liang ◽  
Yong Huang ◽  
Yihui Pan ◽  
Guannan Shu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Expression Patterns ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Proliferation And Metastasis

Abstract Background There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. Method Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. Results Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. Conclusion Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.

scholarly journals LncRNA-LET inhibits cell growth of clear cell renal cell carcinoma by regulating miR-373-3p

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhuo Ye ◽  
Jiachen Duan ◽  
Lihui Wang ◽  
Yanli Ji ◽  
Baoping Qiao
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Luciferase Reporter ◽  
Cell Renal Cell Carcinoma

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with a poor prognosis. LncRNA-LET is a long non-coding RNA (lncRNA) that is down-regulated in ccRCC tissues. However, its role in ccRCC development and progress is unclear. Methods LncRNA-LET expression was detected in ccRCC tissues and ccRCC cells using quantitative real-time PCR. The overexpression and knockdown experiments were performed in ccRCC cells and xenograft mouse model to evaluate role of lncRNA-LET. Cell cycle, apoptosis and JC-1 assays were conducted via flow cytometer. The protein levels were measured through western blot analysis and the interaction between lncRNA-LET and miR-373-3p was identified via luciferase reporter assay. Results LncRNA-LET expression was lower in ccRCC tissues than that in the matched adjacent non-tumor tissues (n = 16). In vitro, lncRNA-LET overexpression induced cell cycle arrest, promoted apoptosis and impaired mitochondrial membrane potential, whereas its knockdown exerted opposite effects. Moreover, we noted that lncRNA-LET may act as a target for oncomiR miR-373-3p. In contrast to lncRNA-LET, miR-373-3p expression was higher in ccRCC tissues. The binding between lncRNA-LET and miR-373-3p was validated. Two downstream targets of miR-373-3p, Dickkopf-1 (DKK1) and tissue inhibitor of metalloproteinase-2 (TIMP2), were positively regulated by lncRNA-LET in ccRCC cells. MiR-373-3p mimics reduced lncRNA-LET-induced up-regulation of DKK1 and TIMP2 levels, and attenuated lncRNA-LET-mediated anti-tumor effects in ccRCC cells. In vivo, lncRNA-LET suppressed the growth of ccRCC xenograft tumors. Conclusion These findings indicate that lncRNA-LET plays a tumor suppressive role in ccRCC by regulating miR-373-3p.

scholarly journals MicroRNA-30a-5p Inhibits the Growth of Renal Cell Carcinoma by Modulating GRP78 Expression

2017 ◽  
Vol 43 (6) ◽  
pp. 2405-2419 ◽  
Author(s):  
Changlin Wang ◽  
Licheng Cai ◽  
Jing Liu ◽  
Gang Wang ◽  
Haoming Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Gene Expression Omnibus ◽  
Negative Regulator ◽  
The Cancer Genome Atlas ◽  
Luciferase Reporter ◽  
Cell Renal Cell Carcinoma

Background/Aims: MiR-30a-5p, a member of the microRNA-30 family (miR-30), is known to function as a tumor suppressor in several different cancers. However, the expression levels, biological function, and underlying mechanisms of miR-30a-5p in renal cell carcinoma (RCC) remain unclear. Glucose-regulated protein78 (GRP78) is a common cancer biomarker and promotes the growth and survival of cancer cells. The expression of GRP78 has been reported to be modulated by miR-30a in neurons. In this study, the expression profile of miR-30a-5p in clear cell renal cell carcinoma (ccRCC) and its effect on ccRCC through regulating GRP78 expression was investigated. Methods: MiR-30a-5p expression was analyzed using bioinformatic software on open microarray datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and confirmed by quantitative RT-PCR (qRT-PCR) in ccRCC cell lines. Cell proliferation was investigated using CCK-8 and cell count assays. Western blotting, immunohistochemistry, luciferase reporter assays, and flow cytometry were employed to investigate the mechanisms of the effect of miR-30a-5p on ccRCC Results: MiR-30a-5p was down-regulated in ccRCC and related to the clinicopathological factors and prognosis of ccRCC. MiR-30a-5p was found to both suppress the growth of ccRCC cells and promote apoptosis of ccRCC cells in vitro. GRP78 was the direct target gene of miR-30a-5p, and the GRP78 expression was inversely correlated with the expression of miR-30a-5p in vivo and in vitro. The functional studies of GRP78 overexpression or knockdown demonstrated that GRP78 promoted proliferation and anti-apoptosis of ccRCC cells, and the oncogenic activity of GRP78 resulting in by miR-30a-5p overexpression. Conclusion: MiR-30a-5p is a bona fide negative regulator of GRP78 expression, and the anti-tumor activity of miR-30a-5p in ccRCC is due at least in part to down-regulating GRP78 expression and modulating the unfolded protein response (UPR) pathway. Thus, miR-30-GRP78 interaction provides a novel therapeutic candidate target in ccRCC treatment.

scholarly journals FMNL1 Exhibits Pro-Metastatic Activity via CXCR2 in Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 10 ◽  
Author(s):  
Mei-Fang Zhang ◽  
Qiu-Li Li ◽  
Yu-Feng Yang ◽  
Yun Cao ◽  
Chris Zhiyi Zhang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Metastasis ◽  
Clear Cell ◽  
Luciferase Reporter ◽  
Cell Renal Cell Carcinoma ◽  
Metastatic Activity

Formin-like (FMNL) proteins are responsible for cytoskeletal remodeling and have been implicated in the progression and spread of human cancers. Yet the clinical significance and biological function of FMNL1 in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, the expression of FMNL1 in ccRCC and its clinical value were determined by tissue microarray-based IHC and statistical analyses. The role of FMNL1 in ccRCC metastasis and the underlying mechanism were investigated via in vitro and in vivo models using gene regulation detection, ChIP, Luciferase reporter assays, and rescue experiments. We show that FMNL1 is upregulated in ccRCC and exhibits pro-metastatic activity via induction of CXCR2. High expression of FMNL1 is significantly correlated with advanced tumor stage, higher pathological tumor grade, tumor metastasis, and unfavorable prognosis in two independent cohorts containing over 800 patients with ccRCC. The upregulation of FMNL1 in ccRCC is mediated by the loss of GATA3. Ectopic expression of FMNL1 promotes, whereas FMNL1 depletion inhibits cell migration in vitro and tumor metastasis in vivo. The FMNL1-enhanced cell mobility is markedly attenuated by the knockdown of CXCR2. Further studies demonstrate that FMNL1 increases the expression of CXCR2 via HDAC1. In clinical samples, FMNL1 expression is positively associated with CXCR2, and is negatively connected to GATA3 expression. Collectively, our data suggest FMNL1 serve as a potential prognostic factor and function as an oncogene. The axis of GATA3/FMNL1/CXCR2 may present a promising therapeutic target for tumor metastasis in ccRCC.

scholarly journals Mir-144-3p Promotes Cell Proliferation, Metastasis, Sunitinib Resistance in Clear Cell Renal Cell Carcinoma by Downregulating ARID1A

2017 ◽  
Vol 43 (6) ◽  
pp. 2420-2433 ◽  
Author(s):  
Wen Xiao ◽  
Ning Lou ◽  
Hailong Ruan ◽  
Lin Bao ◽  
Zhiyong Xiong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Cell Renal Cell Carcinoma

Background/Aims: We previously performed microRNA (miRNA) microarray to identify effective indicators of clear cell renal cell carcinoma (ccRCC) tissue samples and preoperative/postoperative plasma in which we identified miR-144-3p as an oncomiRNA. However, the molecular mechanism of miR-144-3p remains unclear. This study aims to explore the roles of miR-144-3p in the invasion, migration and Sunitinib-resistance in ccRCC and to elucidate the underlying mechanisms. Methods: Gain and loss of function approaches were used to investigate the cell proliferation, cycle distribution, clonogenicity, migration, invasion, chemosensitivity of miR-144-3p in vitro. The xenograft model was used to assess the effects of miR-144-3p overexpression on tumorigenesis. Bioinformatics analysis and dual-luciferase reporter assay were used to indentify AT-rich interactive domain 1A (ARID1A) as a direct target gene of miR-144-3p. Quantitative RT-PCR, Western blotting, and immunohistochemical (IHC) staining were used to explore ARID1A expression level of the mRNA and protein. Results: We found that miR-144-3p overexpression enhanced cell proliferation, clonogenicity, migration, invasion, and chemoresistance in ccRCC cells. Notably, the oncotumor activities of miR-144-3p were mediated by repressing the expression of ARID1A. The downregulation of ARIDIA could promote the function of miR-144-3p in cell proliferation, metastasis and chemoresistance. Consistently, ARID1A mRNA and protein levels were decreased in ccRCC and in nude mice, and they negatively correlated with miR-144-3p. Conclusion: Higher miR-144-3p may enhance malignancy and resistance to Sunitinib in ccRCC by targeting ARID1A, the observations may uncover novel strategies of ccRCC treatment.

scholarly journals Long noncoding RNA LINC00641 promotes renal cell carcinoma progression via sponging microRNA-340-5p

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jianping Zhang ◽  
Shengming Jin ◽  
Wenjun Xiao ◽  
Xuchao Zhu ◽  
Chengyou Jia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Colony Formation ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
Tumor Node Metastasis Stage

Abstract Background Emerging evidences have revealed that long non-coding RNAs (lncRNAs) have played critical roles in tumor occurrence and progression. LINC00641 has been reported to be involved in the initiation and development of several cancers in the recent years. However, the detailed biological role of LINC00641 in renal cell carcinoma (RCC) remains largely unclear. Methods In this study, the expression and biological function of LINC00641 were assessed in renal carcinoma both in vitro and in vivo. Cell proliferation, migration and colony formation assay were performed to explore the effect of LINC00641on growth, progression and invasion of RCC cell. qRT-PCR, flow cytometry and luciferase reporter assay and in vivo tumorigenicity assay were also carried out. Results The expression of LINC00641 was overexpressed in RCC tissues and cell lines, and high LINC00641 expression was correlated with tumor-node-metastasis stage. Furthermore, Silencing of LINC00641 remarkably inhibited the ability of cell proliferation, colony formation, and invasive capacities, as well as increasing the apoptotic rates of RCC cells in vitro. Mechanistically, miR-340-5p was validated to be targeted by LINC00641 and knockdown of miR-340-5p counteracted LINC00641 silencing-mediated inhibition of RCC progression. In addition, in vivo experiment confirmed the findings discovered in vitro. Conclusions These results suggested that LINC00641 promoted the progression of RCC by sponging miR-340-5p.

scholarly journals Blocking Exosomal miR-19b-3p from Renal Cell Carcinoma Cells Enhances Sunitinib Mediated Anti-Tumor Activity via Promoting TGFBR2/KLF10 Expression

2021 ◽  
Author(s):  
Dong Lv ◽  
Taimin Shen ◽  
Juncheng Yao ◽  
Qi Yang ◽  
Ying Xiang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Resistant Cell ◽  
Cell Counting ◽  
Induced Apoptosis ◽  
Related Proteins

Abstract Background Multiple studies have found that microRNAs contribute to the malignant progression and chemoresistance of renal cell carcinoma (RCC). This study intends to probe the effect of miR-19b-3p shuttled by exosomes derived from RCC cells on RCC development and its resistance to Sunitinib. Methods Sunitinib-resistant cell lines (OSRC-2R and Caki-1R) were constructed from OSRC-2 and Caki-1 RCC cells. Exosomes in the RCC cell supernatant were isolated, and the miR-19b-3p profile in cells and exosomes was measured by reverse transcription-polymerase chain reaction (RT-PCR). Subsequently, the TGFβR2/SMAD2/3 pathway was activated by TGFβ, and the KLF10 overexpression and miR-19b-3p overexpression/knockdown models were constructed. The cell counting kit-8 (CCK-8) assay, colony formation assay and flow cytometry were implemented to verify RCC cell proliferation, Sunitinib chemosensitivity, and apoptosis. The expression of apoptosis-related proteins and the TGFβR2-SMAD2/3-KLF10 pathway was monitored by Western blot. MiR-19b-3p was overexpressed in sunitinib-resistant RCC cell lines (OSRC-2R and Caki-1R) and their exosomes (vs. normal OSRC-2 and Caki-1 cell lines). Results In-vitro experiments showed that knocking down cellular and exosomal miR-19b-3p levels reduced the proliferation and colony-forming ability of OSRC-2 and Caki-1 cells and strengthened their apoptosis and sensitivity to Sunitinib. Bioinformatics analysis illustrated that miR-19b-3p targeted TGFβR2 and inhibited TGFβR2/SMAD2/3. Activation of the TGFβR2-SMAD2/3 pathway via TGFβ dampened ORSC-2 and Caki-1 cell proliferation, induced apoptosis, and enhanced their chemosensitivity to Sunitinib. Conclusion Moreover, TGFβ heightened KLF10 expression, and overexpressing KLF10 attenuated miR-19b-3p-mediated carcinogenic effects and resistance to Sunitinib by increasing SMAD2/3 phosphorylation. RCC cell-derived exosomal miR-19b-3p enhances RCC progression and Sunitinib chemoresistance by inactivating TGFβR2-SMAD2/3-KLF10.

ER stress protein GRP78 as a therapeutic target combined with antiangiogenic therapy in renal cell carcinoma.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 428-428
Author(s):  
Kyung Seok Han ◽  
Na Li ◽  
Peter A. Raven ◽  
Estelle Li ◽  
Ladan Fazli ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Er Stress ◽  
Cell Carcinoma ◽  
Therapeutic Target ◽  
Renal Cell ◽  
Antiangiogenic Therapy ◽  
Carcinoma Cells ◽  
Unfolded Proteins ◽  
Induced Apoptosis

428 Background: Antiangiogenic therapy deprives oxygen and nutrition from the tumor. These stresses cause unfolded proteins in tumor cells. Glucose regulated protein 78 (GRP78) binds to unfolded proteins and its subsequent activation suppresses global mRNA translation to protect cells from excessive unfolded proteins. We investigated a potential role of GRP78 as a combined therapeutic target in renal cell carcinoma treated with antiangiogenic therapy. Methods: Renal cell carcinoma cells (Caki-1, Caki-2, UMRC-3, and UMRC-6) were used to investigate the effect of GRP78 knockdown, which was performed by small interfering RNA. Caki-1 xenografts were developed and treated with sunitinib 40mg/kg/day to evaluate in vivo expression of GRP78 during antiangiogenic therapy. Caki-1 cells stably overexpressing GRP78 were developed to investigate the role of GRP78 in cancer cell. Hypoxic stress was induced by 1% hypoxia chamber and hypoglycaemic stress was induced by glucose-free media. Downstream signalling pathways of GRP78 were evaluated by Western blots. Results: In vitro hypoxia and/or glucose deprivation induced GRP78 upregulation in Caki-1 cells. GRP78 was also induced in Caki-1 xenografts treated by sunitinib. Overexpression of GRP78 increased tumor proliferation in hypoxic and/or hypoglycemic stresses by activating PERK/eIF2α pathway and protected tumor cells from stress-induced apoptosis. Knockdown of GRP78 using small interference RNA inhibited cancer cell survival and induced apoptosis in renal cell carcinoma cells in vitro. GRP78 knockdown also sensitized renal cell carcinoma cells to ER stress-induced apoptosis and hypoxic and hypoplycemic stress-induces apoptosis. Conclusions: Antiangiogenic therapy induces ER stress by depriving oxygen and glucose from renal cell carcinoma. ER protein GRP78 has a critical role in protecting renal cell carcinoma cells from hypoxic and hypoglycemic stress induced by antiangiogenic therapy. Knockdown of GRP78 sensitizes RCC cells to apoptotic cell death from anti-angiogenic stresses. Our results suggest that GRP78 is a novel therapeutic target in renal cell carcinoma management.

scholarly journals Doxycycline sensitizes renal cell carcinoma to chemotherapy by preferentially inhibiting mitochondrial translation

2021 ◽  
Vol 49 (10) ◽  
pp. 030006052110443
Author(s):  
Bo Wang ◽  
Jinsong Ao ◽  
Xiaoyan Li ◽  
Weimin Yu ◽  
Dan Yu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Colony Formation ◽  
Underlying Mechanism ◽  
Mechanistic Studies ◽  
Mitochondrial Translation ◽  
Induced Apoptosis

Objectives The anti-cancer activity of doxycycline has been reported in many cancers but not renal cell carcinoma (RCC). This study aimed to determine the efficacy of doxycycline alone and in combination with paclitaxel and analyze the underlying mechanism in RCC. Methods Proliferation, colony formation and apoptosis assays were performed in RCC cell lines after drug treatments. An RCC xenograft mouse model was generated, and tumor growth was monitored. Mechanistic studies focused on mitochondrial translation and functions. Results Doxycycline at clinically achievable concentrations inhibited proliferation and colony formation and induced apoptosis in RCC cell lines. In normal kidney cells, doxycycline at the same concentrations either had no effect or was less effective. The combination index value demonstrated that doxycycline and paclitaxel were synergistic in vitro. Consistently, this combination therapy was significantly more effective than the monotherapy in RCC xenograft mice without causing significant toxicity. Mechanistic studies revealed that doxycycline acts on RCC cells via preferentially inhibiting mitochondrial DNA translation, thereby disrupting multiple mitochondrial complexes and impairing mitochondrial respiration. Conclusions Doxycycline is a useful addition to the treatment strategy for RCC. Our work also highlights the therapeutic value of mitochondrial translation inhibition in sensitizing RCC to chemotherapy.

scholarly journals MicroRNA-497 suppresses renal cell carcinoma by targeting VEGFR-2 in ACHN cells

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Sun Pengcheng ◽  
Wang Ziqi ◽  
Yin Luyao ◽  
Zhu Xiangwei ◽  
Liu Liang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Rt Pcr ◽  
Mapk Signalling ◽  
Regulation Of Proliferation

Abnormal expression of miRNAs contributed to cancers through regulation of proliferation, apoptosis and drug resistance of cancer cells. The present study was designed to investigate the effect of miR-497 on renal cell carcinoma (RCC) and its possible mechanism. Forty paired clear cell RCC (ccRCC) tissues and adjacent normal kidney tissues were obtained from patients, who were not treated by chemotherapy or radiotherapy. RT-PCR was performed to detect expression of miR-497 in the ccRCC tissues. Effects of miR-497 on cell viability, apoptosis, migration and invasion were detected in ACHN cells. Western blotting (WB) was employed to detect the downstream targets of miR-497. We found that miR-497 in ccRCC tissues was decreased. We treated ACHN cells with miR-497 mimics and inhibitors in vitro and found that miR-497 inhibited viability, migration and invasion of ACHN cells. miR-497 promoted ACHN cells’ apoptosis. VEGFR-2 was predicted as a possible target of miR-497. Luciferase reporter assay proved that miR-497 suppressed VEGFR-2 directly by binding to its 3′-UTR. Further studies showed that miR-497 influenced the MEK/ERK and p38 MAPK signalling pathways. Our findings demonstrated that miR-497 could suppress RCC by targeting VEGFR-2.

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