Clinicopathologic features of TDO2 overexpression in renal cell carcinoma

Abstract Background Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme catabolizing tryptophan. Several lines of evidence revealed that overexpression of TDO2 is involved in anoikis resistance, spheroid formation, proliferation, and invasion and correlates with poor prognosis in some cancers. The aim of this research was to uncover the expression and biofunction of TDO2 in renal cell carcinoma (RCC). Methods To show the expression of TDO2 in RCC, we performed qRT-PCR and immunohistochemistry in integration with TCGA data analysis. The interaction of TDO2 with PD-L1, CD44, PTEN, and TDO2 expression was evaluated. We explored proliferation, colony formation, and invasion in RCC cells line affected by knockdown of TDO2. Results RNA-Seq and immunohistochemical analysis showed that TDO2 expression was upregulated in RCC tissues and was associated with advanced disease and poor survival of RCC patients. Furthermore, TDO2 was co-expressed with PD-L1 and CD44. In silico analysis and in vitro knockout of PTEN in RCC cell lines revealed the ability of PTEN to regulate the expression of TDO2. Knockdown of TDO2 suppressed the proliferation and invasion of RCC cells. Conclusion Our results suggest that TDO2 might have an important role in disease progression and could be a promising marker for targeted therapy in RCC.

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Comprehensive analysis of copy number variance and sensitivity to common targeted therapy in clear cell renal cell carcinoma: In silico analysis with in vitro validation

Cancer Medicine ◽

10.1002/cam4.3281 ◽

2020 ◽

Vol 9 (16) ◽

pp. 6020-6029 ◽

Cited By ~ 1

Author(s):

Yuqing Li ◽

Yanyun Shen ◽

Zhidong Zhu ◽

Hui Wen ◽

Chenchen Feng

Keyword(s):

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Renal Cell ◽

Copy Number ◽

Clear Cell ◽

In Silico Analysis ◽

Comprehensive Analysis ◽

Cell Renal Cell Carcinoma ◽

Silico Analysis

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lncRNA 00312 Attenuates Cell Proliferation and Invasion and Promotes Apoptosis in Renal Cell Carcinoma via miR-34a-5p/ASS1 Axis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5737289 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16 ◽

Cited By ~ 1

Author(s):

Jiawei Zeng ◽

Yuanmeng Li ◽

Yaodong Wang ◽

Gang Xie ◽

Qian Feng ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Proliferation ◽

Cell Carcinoma ◽

Renal Cell ◽

Functional Roles ◽

Normal Tissues ◽

Potential Binding Site ◽

Proliferation And Invasion

Background. Previous studies have demonstrated that lncRNAs play functional roles in regulating cancer cell proliferation, invasion, and apoptosis. Recent studies confirmed that lncRNA 00312 has important biological functions in lung and colorectal cancer. However, the role of lncRNA 00312 in renal cell carcinoma (RCC) remains unclear. Our aim was to explore the function of lncRNA 00312 in RCC and its potential molecular mechanism. Methods. RCC cell lines A498 and ACHN were used as in vitro models in this study. RT-PCR was performed to determine lncRNA 00312, miR-34a-5p, and ASS1 mRNA expression. Proliferation and invasion were examined by CCK-8 and Transwell assay to confirm the function role of lncRNA 00312. Western blot analysis was used to examine the expression of apoptotic proteins Bax and Bcl-2. Results. lncRNA was significantly downregulated in RCC cells such as A498 and ACHN; the expression of lncRNA 00312 in RCC tissues was significantly lower than that in adjacent normal tissues. Patients with low expression of lncRNA 00312 have worse prognosis regarding pathological grade, tumor size, and TNM stage. Overexpression of lncRNA 00312 suppressed A498 and ACHN cell proliferation and invasion, while promoting apoptosis. Our study found that miR-34a-5p had the potential binding site with lncRNA 00312 and revealed the role of miR-34a-5p in RCC. Furthermore, we confirmed that lncRNA 00312 played its role with the participation of ASS1 and miR-34a-5p. Conclusion. lncRNA 00312 can inhibit RCC proliferation and invasion and promote apoptosis in vitro by suppressing miR-34a-5p and overexpressing ASS1. Our study demonstrated that the lncRNA 00312/miR-34a-5p/ASS1 axis may play a functional role in the progression of RCC; lncRNA 00312 abundance is a prognostic factor candidate for RCC survival, which provides new insights for RCC clinical treatment.

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Prognostic and Therapeutic Potential of The OIP5 Network in Papillary Renal Cell Carcinoma

10.21203/rs.3.rs-728952/v1 ◽

2021 ◽

Author(s):

Mathilda Chow ◽

Yan Gu ◽

Lizhi He ◽

Xiaozeng Lin ◽

Ying Dong ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Therapeutic Potential ◽

Synthetic Lethality ◽

Papillary Renal Cell Carcinoma ◽

Mrna Levels ◽

Rna Seq

Abstract Background: Papillary renal cell carcinoma (pRCC) is an aggressive but minor type of RCC compared to the main RCC type, clear cell RCC. The current understanding and management of pRCC remain poor. OIP5 possesses oncogenic functions; its contributions to pRCC remain unknown.Methods: OIP5 expression in pRCC at both the protein and mRNA levels was determined using tissue microarray and TCGA dataset. OIP5 was ectopically expressed in metastatic ACHN pRCC cells; xenografts were performed with gene expression profiled by RNA-seq. Differentially expressed genes (DEGs) were analyzed for prognostic potential and impact on pRCC. The effect of PLK1, an OIP5-related DEG, on pRCC tumor growth in vivo was examined.Results: OIP5 expression is upregulated in pRCC. The upregulation associates with pRCC adverse features (T1P<T2P<CIMP, Stage1+2<Stage 3<Stage 4, and N0<N1) and effectively stratifies the fatality risk. OIP5 promotes ACHN pRCC cell proliferation and xenograft formation. RNA-seq reveals network alterations related to immune regulation, metabolism, and hypoxia in ACHN OIP5 tumors compared to empty vector tumors. A set of DEGs was derived from ACHN OIP5 xenografts and primary pRCCs (n=282) contingent to OIP5 upregulation; both DEG sets share 66 overlap genes. Overlap66 effectively predicts overall survival (p<2e-16) and relapse (p<2e-16) possibilities. The prediction is associated with a good out-of-sample performance, supporting its clinical applications. High-risk tumors stratified by Overlap66 risk score possess an immune suppressive environment, evident by elevations in Treg cells and PD1 expression in CD8 T cells. Upregulation of PLK1 occurs in both xenografts and primary pRCC tumors with OIP5 elevations. PLK1 displays a synthetic lethality relationship with OIP5; PLK1 inhibitor BI2356 causes G2/M arrest in ACHN OIP5 cells in vitro and significantly inhibits the growth of xenografts formed by ACHN OIP5 cells in vivo. Conclusions: Our research reveals that OIP5 and its network possess robust prognostic and therapeutic potentials; the prognostic value of Overlap66 and the therapeutic potential of PLK1 inhibitors may pave the way for developing personalized medicine for pRCC management.

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Gelsolin inhibits the proliferation and invasion of the 786-0 clear cell renal cell carcinoma cell line in vitro

Molecular Medicine Reports ◽

10.3892/mmr.2015.4313 ◽

2015 ◽

Vol 12 (5) ◽

pp. 6887-6894 ◽

Cited By ~ 5

Author(s):

XIAOLING ZHU ◽

LIMIN CAI ◽

QINGGANG MENG ◽

XIAOMING JIN

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cell Line ◽

Renal Cell ◽

Clear Cell ◽

Carcinoma Cell ◽

Cell Renal Cell Carcinoma ◽

Renal Cell Carcinoma Cell ◽

Proliferation And Invasion

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MiR-6838-5p enhances the growth and invasion of renal cell carcinoma dependent on DMTF1 via inhibiting the ARF-p53 pathway

10.21203/rs.3.rs-22399/v1 ◽

2020 ◽

Author(s):

Jun Zhao ◽

Xiao-Qiang Zhai ◽

Yan Wu ◽

Dong Zhang ◽

He-Cheng Li ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Proliferation ◽

Epithelial Cells ◽

Cell Carcinoma ◽

Cell Lines ◽

Renal Cell ◽

Renal Epithelial Cells ◽

Normal Tissues ◽

Proliferation And Invasion

Abstract Backgroud: Renal cell carcinoma (RCC) is one of the most common renal malignancies in the urinary system. Numerous studies have demonstrated that miRNAs can regulate tumorigenesis and progression, while the underlying molecular mechanism for miR-6838-5p involved in RCC development is still largely unknown.Methods: The relative expression of miR-6838-5p in RCC tissues, RCC cell lines, adjacent normal tissues and normal renal epithelial cells was detected by reverse transcription polymerase chain reaction (RT-qPCR). In vitro studies, cell proliferation and invasion in human RCC cell lines ACHN and 786-O were evaluated by CCK-8 assay, Transwell assay, Colony formation assay and Flow cytometry. Bioinformatics analysis, luciferase report analysis and Western blot assay were proved that Cyclin D binding myb-like transcription factor 1 (DMTF1) is the target of miR-6838-5p.Results: Our study confirmed that miR-6838-5p was upregulated in RCC tissues (30/42, 77.43%, P < 0.01) and RCC cell lines (P < 0.05) compared to adjacent normal tissues and normal renal epithelial cells. In vitro studies demonstrated that overexpression of miR-6838-5p significantly increased cell proliferation and invasion in human RCC cell lines ACHN and 786-O (P < 0.05), whereas inhibition of miR-6838-5p inhibited cell proliferation and invasion (P < 0.05). Furthermore, we found that miR-6838-5p binds to the wild-type DMTF1 3'UTR. In addition, we found that DMTF1 was downregulation in RCC tissues and cell lines. Meanwhile, it was demonstrated in ACHN cells that overexpression of miR-6838-5p inhibited the expression of DMTF1. Finally, we also confirmed that the interaction of miR-6838-5p overexpression and DMTF1 overexpression might rescue the inhibitory effects of overexpression of miR-6838-5p on the expression of phosphatase and tensin homolog (PTEN), p53, Murine double minute 2 (MDM2) and alternative reading frame (ARF) in the DMTF1-mediated ARF-p53 downstream pathway.Conclusions: Our research shows that miR-6838-5p enhances the growth and invasion of renal cell carcinoma dependent on DMTF1 via inhibiting the ARF-p53 pathway, which suggest that miR-6838-5p can be used as a marker for the diagnosis of RCC.

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miR-216b Post-Transcriptionally Downregulates Oncogene KRAS and Inhibits Cell Proliferation and Invasion in Clear Cell Renal Cell Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000493621 ◽

2018 ◽

Vol 49 (5) ◽

pp. 1755-1765 ◽

Cited By ~ 10

Author(s):

Yan Wang ◽

Daoquan Dong ◽

Shuqi Jiang ◽

Enpu Zhang ◽

Wenzhong Zheng ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Proliferation And Invasion ◽

Ccrcc Cell

Background/Aims: Increasing evidence has shown that miR-216b plays an important role in human cancer progression. However, little is known about the function of miR-216b in renal cell carcinoma. Methods: The expression levels of miR-216b in renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-216b in renal cell carcinoma proliferation and/or metastasis was examined in vitro and in vivo. The target of miR-216b was identified by a dual-luciferase reporter assay. The expression level of KRAS protein was measured by western blotting. Results: The expression of miR-216b was downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the 3’untranslated region (UTR) of KRAS and inhibit the expression of KRAS through translational repression. The in vitro study revealed that miR-216b attenuated ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways. Conclusion: Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC.

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