Downregulation of VEGFA inhibits proliferation, promotes apoptosis, and suppresses migration and invasion of renal clear cell carcinoma

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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Hypoxia regulates the sperm associated antigen 4 (SPAG4) via HIF, which is expressed in renal clear cell carcinoma and promotes migration and invasion in vitro

Molecular Carcinogenesis ◽

10.1002/mc.22065 ◽

2013 ◽

Vol 53 (12) ◽

pp. 970-978 ◽

Cited By ~ 7

Author(s):

Karl Xaver Knaup ◽

Juliana Monti ◽

Thomas Hackenbeck ◽

Tilmann Jobst‐Schwan ◽

Bernd Klanke ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Migration And Invasion

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Inhibition of KIF20A by Transcription Factor IRF6 Affects the Progression of Renal Clear Cell Carcinoma

10.21203/rs.3.rs-136418/v1 ◽

2020 ◽

Author(s):

Xinwei Ma ◽

Xiaoqi Wang ◽

Qian Dong ◽

Hongquan Pang ◽

Jianming Xu ◽

...

Keyword(s):

Transcription Factor ◽

Cell Carcinoma ◽

Renal Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Cell Activity ◽

Renal Clear Cell Carcinoma ◽

Migration And Invasion ◽

Invasion And Migration ◽

And Migration

Abstract Background: Renal clear cell carcinoma (ccRCC) is one of the most common malignant tumors, and its incidence is increasing year by year. IRF6 plays an important role in the occurrence of tumors, but the expression of IRF6 in ccRCC has not been reported so far.Methods: The expression of IRF6 and KIF20A in ccRCC was predicted by GEPIA and HAP database. In addition, the GEPIA database predicted the relationship between the expression of IRF6 and KIF20A and the pathological staging, overall survival, and disease-free survival of ccRCC. The possible binding sites of IRF6 and KIF20A promoters were predicted by JASPAR database and verified by luciferase and ChIP experiments. The specific effects of IRF6 on proliferation invasion and apoptosis of ccRCC were subsequently examined at the cellular level. The expression of IRF6 and KIF20A in ccRCC cell lines was detected by RT-qPCR and western blot. Cell transfection techniques were used to construct IRF6 and KIF20A overexpressed or interfering plasmids. CCK-8 and clone formation assays were used to detect cell activity. Apoptosis was detected by TUNEL assay. Wound healing and Transwell assays detected the ability of cell migration and invasion, respectively.Results: The database predicted that IRF6 expression was down-regulated in renal carcinoma tissues and correlated with poor prognosis. Cell experiments showed that overexpression of IRF6 inhibited proliferation, invasion and migration of ccRCC. In addition, the database predicted that KIF20A was up-regulated in renal carcinoma tissues and associated with prognosis, and cell experiments demonstrated that interference with KIF20A inhibited proliferation, invasion, and migration of ccRCC. Finally, we confirmed that KIF20A is a functional target of IRF6, and KIF20A partially reverses the effects of IRF6 on the proliferation, invasion and migration of ccRCC.Conclusion: Inhibition of KIF20A by transcription factor IRF6 affects the cell proliferation, invasion, migration of renal clear cell carcinoma.

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TRIP13 is identified as a prognosis biomarker for renal clear cell carcinoma and promotes renal cell carcinoma cell proliferation, migration and invasion

BIOCELL ◽

10.32604/biocell.2021.014972 ◽

2021 ◽

Vol 45 (3) ◽

pp. 577-588

Author(s):

Benjiang Qian ◽

Xiaoyan Ying ◽

Guang Yang ◽

Huizhang Li ◽

Jianming Tan

Keyword(s):

Renal Cell Carcinoma ◽

Cell Proliferation ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Carcinoma Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Migration And Invasion ◽

Renal Cell Carcinoma Cell

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

Frontiers in Oncology ◽

10.3389/fonc.2021.725959 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yanxin Lu ◽

Ximian Liao ◽

Tongyu Wang ◽

Xiaowei Hong ◽

Zesong Li

Keyword(s):

Cell Carcinoma ◽

Signaling Pathway ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Akt Signaling ◽

Receiver Operating Curve ◽

Migration And Invasion ◽

Akt Signaling Pathway ◽

Cox Regression Analysis

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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Delayed Pancreatic Metastasis of Renal Clear Cell Carcinoma

Acta Chirurgica Latviensis ◽

10.2478/chilat-2014-0016 ◽

2013 ◽

Vol 13 (2) ◽

pp. 79-80

Author(s):

Zane Simtniece ◽

Gatis Kirsakmens ◽

Ilze Strumfa ◽

Andrejs Vanags ◽

Maris Pavars ◽

...

Keyword(s):

Abdominal Pain ◽

Surgical Treatment ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Primary Tumour ◽

Renal Clear Cell Carcinoma ◽

Pancreatic Metastasis ◽

Distal Pancreatic Resection

Abstract Here, we report surgical treatment of a patient presenting with pancreatic metastasis (MTS) of renal clear cell carcinoma (RCC) 11 years after nephrectomy. RCC is one of few cancers that metastasise in pancreas. Jaundice, abdominal pain or gastrointestinal bleeding can develop; however, asymptomatic MTS can be discovered by follow-up after removal of the primary tumour. The patient, 67-year-old female was radiologically diagnosed with a clinically silent mass in the pancreatic body and underwent distal pancreatic resection. The postoperative period was smooth. Four months after the surgery, there were no signs of disease progression.

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