CPEB4 Inhibit Cell Proliferation via Upregulating p21 mRNA Stability in Renal Cell Carcinoma

Cytoplasmic polyadenylation element-binding protein 4 (CPEB4) has been reported to be dysregulated in a variety of cancers and seems to play paradoxical roles in different cancers. However, the functional roles of CPEB4 in Renal cell carcinoma (RCC) are still unclear. This study aims to explore the role and underlying mechanism of CPEB4 in RCC. We found that the relative expression level of CPEB4 is down-regulated in RCC tissues and cell lines, and the low CPEB4 expression is correlated with short overall and disease-free survival of RCC patients. CPEB4 significantly inhibits RCC tumor growth both in vivo and in vitro. CPEB4 exerts an anti-tumor effect by increasing p21 mRNA stability and inducing G1 cell cycle arrest in RCC. Our data revealed that CPEB4 is a tumor suppressor gene that restrains cell cycle progression upstream of p21 in RCC. These findings revealed that CPEB4 may become a promising predictive biomarker for prognosis in patients with RCC.

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

Cancer Cell International ◽

10.1186/s12935-019-1008-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

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.

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Long Noncoding RNA LINC00460 Facilitates the Proliferation and Metastasis of Renal Cell Carcinoma via PI3K/AKT Signaling Pathway

10.21203/rs.3.rs-483043/v1 ◽

2021 ◽

Author(s):

Feng-Juan Zhou ◽

Sen Meng ◽

Hongmei Yong ◽

Ping-Fu Hou ◽

Min-Le Li ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cell Lines ◽

Renal Cell ◽

Noncoding Rna ◽

Underlying Mechanism ◽

The Cancer Genome Atlas ◽

Akt Pathway

Abstract Renal cell carcinoma (RCC) is one of the most prevalent cancers. Long noncoding RNAs (LncRNAs) have been indicated as a mediator acted in tumorigenesis of RCC. However, the mechanism of LINC00460 on RCC is yet to be investigated. This study aimed to investigate the potential function of LINC00460 and underlying mechanism of RCC. We detected LINC00460 expression in RCC tissues and the prognosis in RCC patients using Gene Expression Profiling Interactive Analysis (GEPIA) website and The Cancer Genome Atlas (TCGA) database. LINC00460 level in normal renal cell line and RCC cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). We study the effects of LINC00460 on proliferation, migration, invasion, apoptosis in RCC cells lines using a series of in vivo and in vitro experiments. RNA sequencing (RNA-seq) analysis for the whole transcriptome was applied to searching potential LINC00460 related signal pathway in RCC. We identified the significant up-regulated expression level of LINC00460 in RCC tissues and cell lines. Elevated LINC00460 was correlated with shorter survival of RCC patients. Overexpression of LINC00460 promoted cell viability, proliferation, invasion and migration, while down-regulation of LINC00460 exerted inhibitory effect on these activities. We crucially identified that LNC00460 promotes development of RCC by influencing the PI3K/AKT pathway. Knockdown of LNC00460 decreased the phosphorylation of AKT and mTOR. The key finding of our study provided a new evidence suggesting that LINC00460 functions as an oncogene in RCC pathogenesis by mediating the PI3K/AKT pathway, which may provide a new target for the treatment of RCC.

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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

Molecular Cancer ◽

10.1186/s12943-021-01314-w ◽

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.

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Synergistic immunotherapeutic effects of Lycium barbarum polysaccharide and interferon-α2b on the murine Renca renal cell carcinoma cell line in vitro and in vivo

Molecular Medicine Reports ◽

10.3892/mmr.2015.4230 ◽

2015 ◽

Vol 12 (5) ◽

pp. 6727-6737 ◽

Cited By ~ 19

Author(s):

SHIYOU CHEN ◽

LUNAN LIANG ◽

YING WANG ◽

JIANHUN DIAO ◽

CHUNXIONG ZHAO ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Carcinoma Cell ◽

Lycium Barbarum ◽

Renal Cell Carcinoma Cell ◽

Lycium Barbarum Polysaccharide ◽

Interferon Α2b

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MicroRNA-373 promotes tumorigenesis of renal cell carcinoma in vitro and in vivo

Molecular Medicine Reports ◽

10.3892/mmr.2017.7443 ◽

2017 ◽

Vol 16 (5) ◽

pp. 7048-7055 ◽

Cited By ~ 5

Author(s):

Yanli Li ◽

Da Zhang ◽

Jiaxiang Wang

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell

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circAMOTL1L Suppresses Renal Cell Carcinoma Growth by Modulating the miR-92a-2-5p/KLLN Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/9970272 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Ling Gao ◽

Xian Shao ◽

Qingqing Yue ◽

Weifei Wu ◽

Xuejuan Yang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Therapeutic Strategy ◽

Underlying Mechanism ◽

Tumor Stage ◽

Circular Rnas ◽

The Novel ◽

Regulatory Functions

Accumulating evidence indicates that the dysregulation of circular RNAs (circRNAs) contributes to tumor progression; however, the regulatory functions of circRNAs in renal cell carcinoma (RCC) remain largely unknown. In this study, the function and underlying mechanism of circAMOTL1L in RCC progression were explored. qRT-PCR showed the downregulation of circAMOTL1L in RCC tissues and cell lines. The decrease in circAMOTL1L expression correlated with the tumor stage, metastasis, and poor prognosis in patients with RCC. Functional experiments revealed that circAMOTL1L inhibited cell proliferation and increased apoptosis in RCC cells. Subcutaneous implantation with circAMOTL1L-overexpressing cells in nude mice decreased the growth ability of the xenograft tumors. Mechanistically, circAMOTL1L served as a sponge for miR-92a-2-5p in upregulating KLLN (killin, p53-regulated DNA replication inhibitor) expression validated by bioinformatics analysis, oligo pull-down, and luciferase assays. Further, reinforcing the circAMOTL1L–miR-92a-2-5p–KLLN axis greatly reduced the growth of RCC in vivo. Conclusively, our findings demonstrate that circAMOTL1L has an antioncogenic role in RCC growth by modulating the miR-92a-2-5p–KLLN pathway. Thus, targeting the novel circAMOTL1L–miR-92a-2-5p–KLLN regulatory axis might provide a therapeutic strategy for RCC.

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GV1001 Induces Apoptosis by Reducing Angiogenesis in Renal Cell Carcinoma Cells Both In Vitro and In Vivo

Urology ◽

10.1016/j.urology.2017.10.038 ◽

2018 ◽

Vol 113 ◽

pp. 129-137 ◽

Cited By ~ 4

Author(s):

Ga Eun Kim ◽

Ae Ryang Jung ◽

Mee Young Kim ◽

Joseph Bada Lee ◽

Ji Houn Im ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Carcinoma Cells

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Long Non-Coding RNA LINC02747 Promotes the Proliferation of Clear Cell Renal Cell Carcinoma by Inhibiting miR-608 and Activating TFE3

Frontiers in Oncology ◽

10.3389/fonc.2020.573789 ◽

2020 ◽

Vol 10 ◽

Author(s):

Xiang Ju ◽

Yangyang Sun ◽

Feng Zhang ◽

Xiaohui Wei ◽

Zhenguo Wang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Histological Grade ◽

Rapid Development ◽

The Cancer Genome Atlas ◽

Cell Renal Cell Carcinoma

With the rapid development of biotechnology, long noncoding RNAs (lncRNAs) have exhibited good application prospects in the treatment of cancer, and they may become new treatment targets for cancer. This study aimed to explore lncRNAs in clear cell renal cell carcinoma (ccRCC). Differentially expressed lncRNAs in 54 pairs of ccRCC tissues and para-carcinoma tissues were analyzed in The Cancer Genome Atlas (TCGA), and the most significant lncRNAs were selected and verified in ccRCC tissues. We found that lncRNA LINC02747 was highly expressed in ccRCC (P < 0.001) and was closely related to high TNM stage (P = 0.006) and histological grade (P = 0.004) and poor prognosis of patients (P < 0.001). In vivo and in vitro experiments confirmed that LINC02747 could promote the proliferation of ccRCC cells. We also found that LINC02747 regulated the proliferation of RCC cells by adsorbing miR-608. Subsequent mechanistic research showed that miR-608 is downregulated in ccRCC (P < 0.001), and overexpression of miR-608 inbibited the proliferation of RCC cells. Moreover, we found that TFE3 is a direct target gene of miR-608. MiR-608 regulated the proliferation of RCC cells by inhibiting TFE3. In conclusion, LINC02747 upregulates the expression of TFE3 by adsorbing miR-608, ultimately promoting the proliferation of ccRCC cells. The above findings indicate that LINC02747 acts as an oncogene in ccRCC and may be developed as a molecular marker for the diagnosis and prognosis of ccRCC. The LINC02747/miR-608/TFE3 pathway may become a new therapeutic target for ccRCC.

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Kinesin Motor Protein KIFC1 Is a Target Protein of miR-338-3p and Is Associated With Poor Prognosis and Progression of Renal Cell Carcinoma

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15213115046567 ◽

2018 ◽

Vol 27 (1) ◽

pp. 125-137 ◽

Cited By ~ 11

Author(s):

Gang Li ◽

Tie Chong ◽

Jie Yang ◽

Hongliang Li ◽

Haiwen Chen

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Therapeutic Target ◽

Renal Cell ◽

Critical Role ◽

Survival Prognosis ◽

Inhibition Of Proliferation ◽

Invasion And Migration

KIFC1 (kinesin family member C1) plays a critical role in clustering of extra centrosomes in various cancer cells and thus could be considered as a promising therapeutic target. However, whether KIFC1 is involved in the procession of renal cell carcinoma (RCC) still remains unclear. In this study, we found that KIFC1 was upregulated in RCC tissues and is responsible for RCC tumorigenesis (p < 0.001). The high expression of KIFC1 correlates with aggressive clinicopathologic parameters. Kaplan‐Meier analysis suggested that KIFC1 was associated with poor survival prognosis in RCC. Silencing KIFC1 dramatically resulted in inhibition of proliferation, delayed the cell cycle at G2/M phase, and suppressed cell invasion and migration in vitro. The antiproliferative effect of KIFC1 silencing was also observed in xenografted tumors in vivo. miR-338-3p could directly bind to the 3′-untranslated region (3′-UTR) of KIFC1, and ectopic miR-338-3p expression mimicked the inhibitory functions of KIFC1 silencing on RCC cells through inactivation of the PI3K/AKT signaling pathway. Therefore, these results revealed that KIFC1 may be a novel biomarker and an effective therapeutic target for the treatment of RCC.

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