Retracted: MicroRNA-99b suppresses human cervical cancer cell activity by inhibiting the PI3K/AKT/mTOR signaling pathway

Cervical cancer is common cancer among women with high morbidity. MicroRNAs (miRs) are involved in the progression and development of cervical cancer. This study aimed to explore the effect of miR-99b-5p (miR-99b) on invasion and migration in cervical cancer through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. The microarray-based analysis was used to screen out differentially expressed miRNAs. Expression of miR-99b, PI3K, AKT, mTOR, and ribosomal protein S6 kinase (p70S6K) was determined in both cervical cancer tissues and paracancerous tissues. Next, alteration of miR-99b expression in cervical cancer was conducted to evaluate levels of PI3K, AKT, mTOR, p70S6K matrix metallopeptidase 2, epithelial cell adhesion molecule, and intercellular adhesion molecule 1, as well as the effect of miR-99b on cell proliferation, invasion, migration, cell cycle distribution, and apoptosis. The results demonstrated that miR-99b expression was decreased and levels of PI3K, AKT, mTOR, and p70S6K were elevated in cervical cancer tissues. More important, overexpressed miR-99b repressed the PI3K/AKT/mTOR signaling pathway, inhibited cell proliferation, invasion, and migration, blocked cell cycle entry, and promoted apoptosis in cervical cancer. These results indicate that miR-99b attenuates the migration and invasion of human cervical cancer cells through downregulation of the PI3K/AKT/mTOR signaling pathway, which provides a therapeutic approach for cervical cancer treatment.     

miR-224-5p inhibits proliferation,migration, and invasion by targeting PIK3R3/AKT3 in uveal melanoma

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Accumulating investigations have identified the aberrant expression of miRNAs (microRNAs) in UM, such as miR-181, miR-20a, miR-144, miR-146a. The purpose of this study is to investigate the biological function of miR-224-5p in UM. The expression of miR-224-5p, PIK3R3, and AKT3 in 30 tumor tissues and paired adjacent noncancerous tissues were analyzed using Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) assays. Cell proliferation assay, transwell assay, and wound healing assay were used to measure the effects of miR-224-5p on the motility of UM in vitro. Western blot analysis and luciferase assays were used to detect the expression of PIK3R3 and AKT3 as miR-224-5p downstream targets. The results of Western blot analysis and qRT-PCR assays indicated that the expression of miR-224-5p was lower in UM tissues compared to normal tissue, while the expression of PIK3R3 and AKT3 were simultaneously increased. Upregulation of miR-224-5p significantly inhibited capacities of proliferation, invasion, and migration of OCM-1A cells and decreased expression of PIK3R3 and AKT3. Luciferase assay demonstrated PIK3R3 and AKT3 as downstream targets of miR-224-5p. Moreover, upregulating PIK3R3 and AKT3 restrained miR-224-5p-induced inhibition of the motility of OCM-1A cells. Thus, our study proved that miR-224-5p was involved in proliferation, invasion, and migration of UM cells via regulation the expression of PIK3R3 and AKT3. And the results also established a miR-224-5p/PIK3R3/PI3K/AKT axis in the regulation of UM progression, providing an experimental basis for further exploring the miR-224-5p as a therapeutic and diagnosis target for patients with UM.     

MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1

MicroRNAs (miRNAs) have been demonstrated to affect the biological processes of cancers and showed great potential for prognostic biomarkers. In this study, we screened differentially expressed miRNAs in ccRCC based on three dimensions of metastasis, prognosis, and differential expression compared to normal tissue using bioinformatics algorithms. MiR-153-5p was identified as a candidate miRNA to promote ccRCC occurrence and progression. Clinically, we found that miR-153-5p was significantly upregulated and related to unfavorable clinical features in ccRCC. Besides, miR-153-5p served as an independent prognostic biomarker. Functionally, miR-153-5p depletion remarkably inhibited the proliferation and metastasis of ccRCC via the phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Furthermore, AGO1 was proved to be a direct target of miR-153-5p. AGO1 is associated with favorable clinical features and exhibited independent prognostic value in ccRCC. Besides, we observed that AGO1 knockdown significantly promoted tumor proliferation and metastasis. Downregulation of AGO1 partly abolished the oncogenic effects of miR-153-5p knockdown. Furthermore, miR-153-5p combined with AGO1 showed more robust prognostic significance in ccRCC. In conclusion, we found that the newly identified miR-153-5p/AGO1 axis was responsible for tumor occurrence and progression via PI3K/Akt signaling, which may therefore provide promising therapeutic targets and prognostic biomarkers for patients with ccRCC.Subject terms: Cancer screening, miRNAs     

FoxP3-miR-150-5p/3p suppresses ovarian tumorigenesis via an IGF1R/IRS1 pathway feedback loop

Ovarian cancer (OC) causes more deaths than any other gynecological cancer. Many cellular pathways have been elucidated to be associated with OC development and progression. Specifically, the insulin-like growth factor 1 receptor/insulin receptor substrate 1 (IGF1R/IRS1) pathway participates in OC development. Moreover, accumulating evidence has shown that microRNA deregulation contributes to tumor initiation and progression. Here, our study aimed to investigate the molecular functions and regulatory mechanisms of miR-150, specifically, in OC. We found that the expression of miR-150-5p/3p and their precursor, mir-150, was downregulated in OC tissues; lower mir-150 levels were associated with poor OC patient outcomes. Ectopic mir-150 expression inhibited OC cell growth and metastasis in vitro and in vivo. Furthermore, both IRS1 and IGF1R were confirmed as direct targets of miR-150-5p/3p, and the miR-150-IGF1R/IRS1 axis exerted antitumor effects via the PI3K/AKT/mTOR pathway. Forkhead box protein 3 (FoxP3) positively regulated the expression of miR-150-5p/3p by binding to the mir-150 promoter. In turn, the PI3K/AKT/mTOR pathway downregulated FoxP3 and miR-150-5p/3p. Taken together, these findings indicate that a complex FoxP3-miR-150-IGF1R/IRS1-PI3K/AKT/mTOR feedback loop regulates OC pathogenesis, providing a novel mechanism for miR-150 as a tumor suppressor miRNA in OC.Subject terms: Cancer, Translational research     

Downregulation of hsa_circ_0001681 suppresses epithelial-mesenchymal transition in thyroid carcinoma via targeting to miR-942-5p/TWIST1 signaling pathway

Thyroid carcinoma (TC) seriously threatens the health and safety of patients, and the treatment target of it still is poor. RT-qPCR and Western blot were carried out to detect the expression of genes and proteins, respectively. Cell proliferation was confirmed using colony formation assay. Transwell assay were performed to measure the cell migration and invasion. Besides, luciferase reporter assay was accomplished to ensure the target relationship between miR-942-5p and TWIST1 mRNA as well as hsa_circ_0001681. Here, we proved that hsa_circ_0001681 was increased in TC, and located majorly in the cytoplasm of TC cells. However,  miR-942-5p was decreased in TC, and was negatively correlated with hsa_circ_0001681 expression. Knockdown of hsa_circ_0001681 significantly repressed the proliferation, migration, invasion and EMT of TC cells. We also found that the process of hsa_circ_0001681 silencing limited EMT, which was obstructed by TWIST1 increasing. Moreover, hsa_circ_0001681 acted as a miRNA sponge and completed with TWIST1 mRNA for binding to miR-942-5p, thus downregulation of hsa_circ_0001681 repressed EMT and subsequent malignant phenotype of TC cells through targeting miR-942-5p/TWIST1 signaling pathway. Finally, the studies in vivo showed that decreasing of hsa_circ_0001681 effectively inhibited the growth of tumor via repressing EMT by regulating miR-942-5p/TWIST1 signaling pathway. Overall, silencing of hsa_circ_0001681 significantly suppressed TC progression through inhibiting EMT via acting as a miR-942-5p sponge to facilitate the expression of TWIST1. Our data provided a reliable evidence for hsa_circ_0001681 is a potential treatment target in TC.

     

Retracted: Downregulated microRNA-135a ameliorates rheumatoid arthritis by inactivation of the phosphatidylinositol 3-kinase/AKT signaling pathway via phosphatidylinositol 3-kinase regulatory subunit 2

Synovial fibroblasts (SFs) of rheumatoid arthritis (RA) are phenotypically aggressive, typically progressing into arthritic cartilage degradation. Throughout our study, we made explorations into the effects of microRNA-135a (miR-135a) on the SFs involved in RA by mediating the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway via regulation of phosphatidylinositol 3-kinase regulatory subunit 2 (PIK3R2). The expression of PI3K was higher, the expression of PIK3R2 was lower, and AKT was phosphorylated in the RA synovial tissues, relative to the levels found in the normal synovial tissues. We predicted miR-135a to be a candidate miR targeting PIK3R2 using an online website, microRNA.org, which was verified with a dual-luciferase reporter gene assay. Subsequently, high miR-135a expression was observed in RA synovial tissues. To study the effect of the interaction between miR-135a and PIK3R2 in RA, the SFs isolated from RA samples were cultured and transfected with mimic, inhibitor, and small interfering RNA. The proliferation, invasion, and apoptosis of the SFs were detected after the transfection. The cells transfected with miR-135a inhibitor showed inhibited cell proliferation, migration, and invasion, while also displaying promoted cell apoptosis, G0/G1 cell ratio, and decreased S cell ratio, through upregulation of PIK3R2 and inactivation of the PI3K/AKT signaling pathway. These findings provided evidence that downregulation of miR-135a inhibits proliferation, migration, and invasion and promotes apoptosis of SFs in RA by upregulating the PIK3R2 coupled with inactivating the PI3K/AKT signaling pathway. The downregulation of miR-135a might be a potential target in the treatment of RA.     

Circular RNA circPPP6R3 upregulates CD44 to promote the progression of clear cell renal cell carcinoma via sponging miR-1238-3p

Circular RNAs (circRNAs) are a type of covalently closed circular-formed RNAs and play crucial roles in the oncogenesis and progression of various human cancers. Here we identified a novel circRNA, circPPP6R3, to be highly expressed both in clear cell renal cell carcinoma (ccRCC) tissues and cell lines based on analyzing high-throughput sequencing data and qRT-PCR analysis. Highly expressed circPPP6R3 was positively correlated with higher histological grade, T stage, and M stage as well as advanced clinical stage of ccRCC patients. Functionally, knockdown of circPPP6R3 attenuated the proliferation, migration, and invasion of ccRCC cells whereas overexpression had the reverse effects. Mechanistically, the biotin-labeled pull-down assay and dual-luciferase reporter assay revealed that circPPP6R3 directly interacted with miR-1238-3p. miR-1238-3p inhibitors had a rescue effect on the proliferative and metastatic capacities by knockdown of circPPP6R3. Moreover, RNA-sequencing analysis and dual-luciferase reporter assay indicated that circPPP6R3 upregulated CD44, a cell-surface glycoprotein contributed to the cell adhesion and metastasis, via sponging to miR-1238-3p. Further investigation revealed that MMP9 and Vimentin were regulated by CD44 in ccRCC. Our study thus provided evidence that the regulatory network involving circPPP6R3/miR-1238-3p/CD44 axis might provide promising biomarkers as well as a therapeutic approach for ccRCC.Subject terms: Tumour biomarkers, Renal cell carcinoma, Epithelial-mesenchymal transition, Non-coding RNAs     

Circular RNA hsa_circ_101555 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-145-5p and regulating CDCA3 expression

Circular RNAs have been reported to play significant roles in regulating pathophysiological processes while also guiding clinical diagnosis and treatment of hepatocellular carcinoma (HCC). However, only a few circRNAs have been identified thus far. Herein, we investigated the role of a specific closed-loop structure of hsa_circ_101555 that was generated by back-splicing of the host gene casein kinase 1 gamma 1 (CSNK1G1) in the development and proliferation of HCC. We investigated the expression of Hsa_circ_101555 in HCC and normal tissues using bioinformatics. The expression level of hsa_circ_101555 was further detected by fluorescence in situ hybridization and qRT-PCR in ten HCC patients. Transwell, migration, WST-1 assays, and colony formation assays were used to evaluate the role of hsa_circ_101555 in HCC development and proliferation. The regulatory mechanisms of hsa_circ_101555 in miR-145-5p and CDCA3 were determined by dual luciferase reporter assay. A mouse xenograft model was also used to determine the effect of hsa_circ_101555 on HCC growth in vivo. hsa_circ_101555 showed greater stability than the linear RNA; while in vitro and in vivo results demonstrated that hsa_circ_101555 silencing significantly suppressed cell proliferation, migration, and invasion of HCC cells. Rescue experiments further demonstrated that suppression of miR-145-5p significantly attenuated the biological effects of hsa_circ_101555 knockdown in HCC cells. We also identified a putative oncogene CDCA3 as a potential miR-145-5p target. Thus, our results demonstrated that hsa_circ_101555 might function as a competing endogenous RNA of miR-145-5p to upregulate CDCA3 expression in HCC. These findings suggest that hsa_circ_101555 may be a potential therapeutic target for patients with HCC.Subject terms: Liver cancer, Long non-coding RNAs     

Autophagy-associated circular RNA hsa_circ_0007813 modulates human bladder cancer progression via hsa-miR-361-3p/IGF2R regulation

Circular RNAs (circRNAs) drive several cellular processes including proliferation, survival, and differentiation. Here, we identified a circRNA hsa_circ_0007813, whose expression was upregulated in bladder cancer. High hsa_circ_0007813 expression was associated with larger tumor size, higher primary tumor T stage, and higher pathologic grade. Survival analysis showed that patients with high hsa_circ_0007813 expression levels had a poorer prognosis. Based on these findings from clinical tissue samples and cell lines, we assumed that hsa_circ_0007813 functioned a vital role in bladder cancer progression. Next, functional experiments revealed that knockdown of hsa_circ_0007813 inhibited proliferation, migration, and invasiveness of bladder cancer cells both in vitro and in vivo. Through extensive bioinformatic prediction and RNA pull-down assays, we identified hsa-miR-361-3p as a competing endogenous RNA of hsa_circ_0007813. Further bioinformatic studies narrowed targets to 35 possible downstream genes. We then found that knockdown of hsa_circ_0007813 led to altered cell autophagy, bringing our attention to IGF2R, one of the possible downstream genes. IGF2R was also known as cation-independent mannose-6-phosphate receptor (CI-M6PR), was discovered to participate in both autophagy and tumor biology. Regarding autophagy has a dominant role in the survival of tumor cells overcoming cellular stress and correlates with tumor progression, investigations were made to prove that hsa_circ_0007813 could regulate IGF2R expression via hsa-miR-361-3p sponging. The potential of hsa_circ_0007813 in regulating IGF2R expression explained its influence on cell behavior and clinical outcomes. Collectively, our data could offer new insight into the biology of circRNA in bladder cancer.Subject terms: Cancer metabolism, Bladder cancer, Macroautophagy, Cell growth, Cell invasion     

Circular RNA hsa_circ_0000263 participates in cervical cancer development by regulating target gene of miR-150-5p

Circular RNA (circRNA) is a new class of noncoding RNA, and plays an important role in many pathological processes. Cervical cancer is the most common gynecologic malignant tumor. Recently, studies have shown that there is a variety of circRNA involved in the pathogenesis of cervical cancer. We screened out the highly expressed hsa_circ_0000263 from GSE102686 by the quantitative real-time polymerase chain reaction assay in cervical cancer cell lines. In this study, we investigated whether hsa_circ_0000263 might affect cell proliferation, migration, cell cycle and apoptosis in cervical cancer in vitro and in vivo. The luciferase reporter assay and RNA immunoprecipitation assay confirmed the direct interaction between miR-150-5p and hsa_circ_0000263. By using western blot and immunohistochemistry, we confirmed that hsa_circ_0000263 can regulate the expression of murine double minute 4 (MDM4) by affecting miR-150-5p, and finally affect the expression of p53 gene. We found that hsa_circ_0000263 was significantly upregulated in cervical cancer cells. In addition, the knockdown of hsa_circ_0000263, would inhibit cell proliferation and migration ability. In conclusion, our current research reveals the important role of hsa_circ_0000263/miR-150-5p/MDM4/p53 regulatory network in cervical cancer and provides a new insight into the pathogenesis of cervical cancer.     

Inhibition of miR-21-5p suppresses high glucose-induced proliferation and angiogenesis of human retinal microvascular endothelial cells by the regulation of AKT and ERK pathways via maspin

The aim of the present study is to investigate the role of miR-21-5p in angiogenesis of human retinal microvascular endothelial cells (HRMECs). HRMECs were incubated with 5 mM glucose, 30 mM glucose or 30 mM mannitol for 24 h, 48 h or 72 h. Then, HRMECs exposed to 30 mM glucose were transfected with miR-21-5p inhibitor. We found that high glucose increased the expression of miR-21-5p, VEGF, VEGFR2 and cell proliferation activity. Inhibition of miR-21-5p reduced high glucose-induced proliferation, migration, tube formation of HRMECs, and reversed the decreased expression of maspin as well as the abnormal activation of PI3K/AKT and ERK pathways. Down-regulation of maspin by siRNA significantly increased the activities of PI3K/AKT and ERK pathways. In conclusion, inhibition of miR-21-5p could suppress high glucose-induced proliferation and angiogenesis of HRMECs, and these effects may partly dependent on the regulation of PI3K/AKT and ERK pathways via its target protein maspin.     

Circular RNA hsa_circ_0053277 promotes the development of colorectal cancer by upregulating matrix metallopeptidase 14 via miR-2467-3p sequestration

Colorectal cancer (CRC), a kind of human gastrointestinal cancer, has been reported to be one of the most common malignant tumors worldwide. Increasing evidence has indicated that circular RNAs exert significant effects on the development of multiple cancers. Nevertheless, whether hsa_circ_0053277 regulates the progression of CRC remains to be explored. In this study, our results showed that the expression of hsa_circ_0053277 was markedly upregulated in CRC tissues and cells. Knockdown of hsa_circ_0053277 inhibited cell proliferation, migration, and epithelial-mesenchymal transition (EMT) process in CRC. miR-2467-3p had a binding site for hsa_circ_0053277. Molecular mechanism assays confirmed that hsa_circ_0053277 could bind with miR-2467-3p. In addition, hsa_circ_0053277 accelerated cell proliferation rate by acting as a sponge for miR-2467-3p in CRC. Matrix metalloproteinase 14 (MMP14) expression was notably upregulated in CRC cells and MMP14 was a downstream target gene of miR-2467-3p. Besides, hsa_circ_0053277 positively regulated MMP14 expression while miR-2467-3p negatively regulated MMP14 expression. Rescue assays verified that MMP14 knockdown countervailed the function of miR-2467-3p inhibitor on cell proliferation, migration, and EMT process in CRC. To sum up, hsa_circ_0053277 facilitated the development of CRC by sponging miR-2467-3p to upregulate MMP14 expression.     

Timosaponin AIII inhibits metastasis of renal carcinoma cells through suppressing cathepsin C expression by AKT/miR-129-5p axis

Timosaponin AIII (TSAIII) is a steroidal saponin that exerts anticancer activity on various cancer cells. In this study, we explore the effects of TSAIII on renal cell carcinoma (RCC) cells. Our findings show that TSAIII treatment (<8 μM) insignificantly influenced cell viability and cell cycle distribution of human RCC cell lines 786-O, A-498, and ACHN. Further observations revealed that TSAIII inhibited migration and invasion of 786-O and A-498 cells, as well as significantly decreased the production and expression of cathepsin C (CTSC) in both the cell types. Kinase cascade analysis exhibited that PI3K/AKT activation was inhibited, but PTEN expression was increased, in response to TSAIII treatments. Combining TSAIII and PI3K inhibitors, LY294002 synergically reduced the migration and invasion of 786-O and A-498 cells, as well as decreased the CTSC expression in both the cell types. We also observed that miR-129-5p bound to CTSC gene and suppressed the expression of CTSC and demonstrated that the miR-129-5p expression was synergically enhanced by TSAIII and LY294002. In addition, pretreatment with antago-miR-129-5p significantly restored the CTSC expression and the migration and invasion of TSAIII-treated 786-O cells. In conclusion, our findings reveal that TSAIII inhibits the metastatic properties of RCC cells, contributing to the inhibition of PI3K/AKT and the increase of miR-129-5p and the subsequent downregulation of CTSC. This suggests that TSAIII has significant antimetastatic activity against RCC cells and may be beneficial to RCC treatments.     

Retracted: Targeting of SPP1 by microRNA-340 inhibits gastric cancer cell epithelial–mesenchymal transition through inhibition of the PI3K/AKT signaling pathway

Gastric cancer (GC) is a common heterogeneous disease. The critical roles of microRNA-340 (miR-340) in the development and progression of GC were emphasized in accumulating studies. This study aims to examine the regulatory mechanism of miR-340 in GC cellular processes. Initially, microarray technology was used to identify differentially expressed genes and regulatory miRs in GC. After that, the potential role of miR-340 in GC was determined via ectopic expression, depletion, and reporter assay experiments. Expression of secreted phosphoprotein 1 (SPP1), miR-340, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, and epithelial–mesenchymal transition (EMT)-related genes was measured. Moreover, to further explore the function of miR-340 in vivo and in vitro, proliferation, apoptosis, migration, invasion, and tumorigenic capacity were evaluated. SPP1 was a target gene of miR-340 which could then mediate the PI3K/AKT signaling pathway by targeting SPP1 in GC. Furthermore, miR-340 levels were reduced and SPP1 was enriched in GC tissues and cells, with the PI3K/AKT signaling pathway being activated. Inhibitory effects of upregulated miR-340 on SPP1 and the PI3K/AKT signaling pathway were confirmed in vivo and in vitro. Overexpression of miR-340 or the silencing of SPP1 inhibited GC cell proliferation, invasion, migration, and EMT process, but promoted apoptosis of GC cells. Typically, targeting of SPP1 by miR-340 may contribute to the inhibition of proliferation, migration, invasion, and EMT of GC cells via suppression of PI3K/AKT signaling pathway.     

LncRNA Bmp1 promotes the healing of intestinal mucosal lesions via the miR-128-3p/PHF6/PI3K/AKT pathway

Intestinal mucosal injuries are directly or indirectly related to many common acute and chronic diseases. Long non-coding RNAs (lncRNAs) are expressed in many diseases, including intestinal mucosal injury. However, the relationship between lncRNAs and intestinal mucosal injury has not been determined. Here, we investigated the functions and mechanisms of action of lncRNA Bmp1 on damaged intestinal mucosa. We found that Bmp1 was increased in damaged intestinal mucosal tissue and Bmp1 overexpression was able to alleviate intestinal mucosal injury. Bmp1 overexpression was found to influence cell proliferation, colony formation, and migration in IEC-6 or HIEC-6 cells. Moreover, miR-128-3p was downregulated after Bmp1 overexpression, and upregulation of miR-128-3p reversed the effects of Bmp1 overexpression in IEC-6 cells. Phf6 was observed to be a target of miR-128-3p. Furthermore, PHF6 overexpression affected IEC-6 cells by activating PI3K/AKT signaling which was mediated by the miR-128-3p/PHF6 axis. In conclusion, Bmp1 was found to promote the expression of PHF6 through the sponge miR-128-3p, activating the PI3K/AKT signaling pathway to promote cell migration and proliferation.Subject terms: Cell growth, Cell migration     

Circular RNA circDVL1 inhibits clear cell renal cell carcinoma progression through the miR-412-3p/PCDH7 axis

Clear cell renal cell carcinoma (ccRCC) is a primary kidney cancer with high aggressive phenotype and extremely poor prognosis. Accumulating evidence suggests that circular RNAs (circRNAs) play pivotal roles in the occurrence and development of various human cancers. However, the expression, clinical significance and regulatory role of circRNAs in ccRCC remain largely unclear. Here we report that circDVL1 to be reduced in the serums and tissues from ccRCC patients, and to negatively correlate with ccRCC malignant features. Overexpression of circDVL1 inhibits proliferation, induces G1/S arrest, triggers apoptosis, and reduces migration and invasion in different ccRCC cells in vitro. Correspondingly, circDVL1 overexpression suppresses ccRCC tumorigenicity in a mouse xenograft model. Mechanistically, circDVL1 serves as a sponge for oncogenic miR-412-3p, thereby preventing miR-412-3p-mediated repression of its target protocadherin 7 (PCDH7) in ccRCC cells. Collectively, our results demonstrate that circDVL1 exerts tumor-suppressive function during ccRCC progression through circDVL1/miR-412-3p/PCDH7 axis, and suggest that circDVL1 could be a novel diagnostic and prognositc marker and therapeutic target for ccRCC.