The Clinical Relevance and Tumor Promoting Function of C19orf10 in Kidney Renal Clear Cell Carcinoma

Kidney renal clear cell carcinoma (KIRC) is the most common primary renal neoplasms. Currently, there are few molecular indicators and therapeutic targets that can be used in diagnostic and prognostic assessment. In this study, we identified the C19orf10 expression in KIRC specimens and explored the diagnostic and prognostic value of C19orf10 in KIRC using TCGA and CPTAC database. Loss-of- and gain-of- function of C19orf10 was performed to investigate the roles of C19orf10 on KIRC cell viability, proliferation, migration and invasion via CCK-8, Edu incorporation and Transwell assays respectively. C19orf10 was overexpressed in KIRC tissues and the elevated C19orf10 expression was closely associated with clinicopathological characteristics of KIRC including histological grade, TNM stage, metastatic status. Silencing C19orf10 significantly suppressed the viability, proliferation, migration and invasion ability, while overexpression of C19orf10 promoted the progression and malignant phenotype in KIRC cells. Furthermore, C19orf10 exerted its carcinogenic function by regulating ZO-1 and PTEN/Akt signaling pathway. Moreover, the Kaplan–Meier survival analysis, Cox regression analysis and receiver operating curve analysis showed that patients with C19orf10 overexpression have poor survival time. C19orf10 could discriminate KIRC patients with high-risk from low-risk. Taken together, C19orf10 contributes to KIRC development via ZO-1 and PTEN/Akt signaling pathway and C19orf10 could serve as a potential diagnostic and prognostic candidate and therapeutic target of KIRC.

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LncRNA CDKN2B-AS1 stabilized by IGF2BP3 drives the malignancy of renal clear cell carcinoma through epigenetically activating NUF2 transcription

Cell Death and Disease ◽

10.1038/s41419-021-03489-y ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Xina Xie ◽

Jiatian Lin ◽

Xiaoqin Fan ◽

Yuantang Zhong ◽

Yequn Chen ◽

...

Keyword(s):

Cell Carcinoma ◽

Survival Data ◽

Kinase Inhibitor ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Binding Protein ◽

Renal Clear Cell Carcinoma ◽

Receiver Operating Curve ◽

Migration And Invasion ◽

Integrated Analysis

AbstractBecause of the lack of sensitivity to radiotherapy and chemotherapy, therapeutic options for renal clear cell carcinoma (KIRC) are scarce. Long noncoding RNAs (lncRNAs) play crucial roles in the progression of cancer. However, their functional roles and upstream mechanisms in KIRC remain largely unknown. Exploring the functions of potential essential lncRNAs may lead to the discovery of novel targets for the diagnosis and treatment of KIRC. Here, according to the integrated analysis of RNA sequencing and survival data in TCGA-KIRC datasets, cyclin-dependent kinase inhibitor 2B antisense lncRNA (CDKN2B-AS1) was discovered to be the most upregulated among the 14 lncRNAs that were significantly overexpressed in KIRC and related to shorter survival. Functionally, CDKN2B-AS1 depletion suppressed cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, CDKN2B-AS1 exerted its oncogenic activity by recruiting the CREB-binding protein and SET and MYND domain-containing 3 epigenetic-modifying complex to the promoter region of Ndc80 kinetochore complex component (NUF2), where it epigenetically activated NUF2 transcription by augmenting local H3K27ac and H3K4me3 modifications. Moreover, we also showed that CDKN2B-AS1 interacted with and was stabilized by insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an oncofetal protein showing increased levels in KIRC. The Kaplan–Meier method and receiver operating curve analysis revealed that patients whose IGF2BP3, CDKN2B-AS1 and NUF2 are all elevated showed the shortest survival time, and the combined panel (containing IGF2BP3, CDKN2B-AS1, and NUF2) possessed the highest accuracy in discriminating high-risk from low-risk KIRC patients. Thus, we conclude that the stabilization of CDKN2B-AS1 by IGF2BP3 drives the malignancy of KIRC through epigenetically activating NUF2 transcription and that the IGF2BP3/CDKN2B-AS1/NUF2 axis may be an ideal prognostic and diagnostic biomarker and therapeutic target for KIRC.

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HOXA6 inhibits cell proliferation and induces apoptosis by suppressing the PI3K/Akt signaling pathway in clear cell renal cell carcinoma

International Journal of Oncology ◽

10.3892/ijo.2019.4789 ◽

2019 ◽

Cited By ~ 2

Author(s):

Feixiang Wu ◽

Shasha Wu ◽

Hang Tong ◽

Weiyang He ◽

Xin Gou

Keyword(s):

Renal Cell Carcinoma ◽

Cell Proliferation ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Renal Cell ◽

Clear Cell ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Cell Renal Cell Carcinoma

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Identification of a Prognostic Risk Signature of Kidney Renal Clear Cell Carcinoma Based on Regulating the Immune Response Pathway Exploration

Journal of Oncology ◽

10.1155/2020/6657013 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Guangzhen Wu ◽

Yingkun Xu ◽

Chenglin Han ◽

Zilong Wang ◽

Jiayi Li ◽

...

Keyword(s):

Immune Response ◽

Cell Carcinoma ◽

Sensitivity And Specificity ◽

Cox Regression ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Lasso Regression ◽

Regression Curve ◽

Cox Regression Analysis

Purpose. To construct a survival model for predicting the prognosis of patients with kidney renal clear cell carcinoma (KIRC) based on gene expression related to immune response regulation. Materials and Methods. KIRC mRNA sequencing data and patient clinical data were downloaded from the TCGA database. The pathways and genes involved in the regulation of the immune response were identified from the GSEA database. A single factor Cox analysis was used to determine the association of mRNA in relation to patient prognosis P < 0.05 . The prognostic risk model was further established using the LASSO regression curve. The survival prognosis model was constructed, and the sensitivity and specificity of the model were evaluated using the ROC curve. Results. Compared with normal kidney tissues, there were 28 dysregulated mRNA expressions in KIRC tissues P < 0.05 . Univariate Cox regression analysis revealed that 12 mRNAs were related to the prognosis of patients with renal cell carcinoma. The LASSO regression curve drew a risk signature consisting of six genes: TRAF6, FYN, IKBKG, LAT2, C2, IL4, EREG, TRAF2, and IL12A. The five-year ROC area analysis (AUC) showed that the model has good sensitivity and specificity (AUC >0.712). Conclusion. We constructed a risk prediction model based on the regulated immune response-related genes, which can effectively predict the survival of patients with KIRC.

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miR‐138‐5p inhibits proliferation and invasion in kidney renal clear cell carcinoma by targeting SINA3 and regulation of the Notch signaling pathway

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.23766 ◽

2021 ◽

Author(s):

Yang Liu ◽

Hong‐chen Qu

Keyword(s):

Notch Signaling ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Notch Signaling Pathway ◽

Renal Clear Cell Carcinoma ◽

Proliferation And Invasion

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MicroRNA-203 inhibits epithelial-mesenchymal transition, migration, and invasion of renal cell carcinoma cells via the inactivation of the PI3K/AKT signaling pathway by inhibiting CAV1

Cell Adhesion & Migration ◽

10.1080/19336918.2020.1827665 ◽

2020 ◽

Vol 14 (1) ◽

pp. 227-241

Author(s):

Ning Han ◽

Hai Li ◽

Hui Wang

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Renal Cell ◽

Epithelial Mesenchymal Transition ◽

Akt Signaling ◽

Carcinoma Cells ◽

Migration And Invasion ◽

Akt Signaling Pathway ◽

Mesenchymal Transition

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PAR-2 promotes cell proliferation, migration, and invasion through activating PI3K/AKT signaling pathway in oral squamous cell carcinoma

Bioscience Reports ◽

10.1042/bsr20182476 ◽

2019 ◽

Vol 39 (7) ◽

Cited By ~ 3

Author(s):

Kai-Liang Tang ◽

Han-Ying Tang ◽

Yi Du ◽

Tian Tian ◽

Shi-Jiang Xiong

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Squamous Cell ◽

Mrna Level ◽

Akt Signaling ◽

Akt Pathway ◽

Migration And Invasion ◽

Akt Signaling Pathway

AbstractObjective: This research aimed to explore the function of protease activated receptor 2 (PAR-2) in oral squamous cell carcinoma (OSCC) development and progression, as well as underlying molecular mechanism.Methods: Tissue samples were collected from 115 OSCC patients. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of PAR-2 mRNA in OSCC tissues and cells. MTT and Transwell assays were used to detect the proliferation, migration, and invasion of OSCC cells, respectively. Western blot was performed to determine protein expression.Results: The expression of PAR-2 mRNA was up-regulated in OSCC tissue and cells (P<0.01), and its mRNA level was obviously correlated to tumor differentiation and TNM stage in OSCC (P<0.05 for both). The activation of PAR-2 with PAR-2AP (PAR-2 agonist) significantly promoted the proliferation, migration, and invasion of OSCC cells, while its knockout could inhibit malignant behaviors of OSCC cells (P<0.05). Excessive activation of PAR-2 enhanced phosphorylation level of PI3K, AKT, and mTOR revealing the activation of PI3K/AKT pathway. Moreover, LY294002, the inhibitor of PI3K/AKT pathway, could reverse oncogenic action caused by PAR-2 activation.Conclusion: PAR-2 can promote OSCC growth and progression via activating PI3K/AKT signaling pathway.

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