scholarly journals TRIM44 promotes cell proliferation and migration by inhibiting FRK in renal cell carcinoma

2020 ◽  
Vol 111 (3) ◽  
pp. 881-890 ◽  
Author(s):  
Yuta Yamada ◽  
Naoki Kimura ◽  
Ken‐ichi Takayama ◽  
Yusuke Sato ◽  
Takashi Suzuki ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Neuropilin 1 and Neuropilin 2 Gene Invalidation or Pharmacological Inhibition Reveals Their Relevance for the Treatment of Metastatic Renal Cell Carcinoma

2020 ◽  
Author(s):  
Aurore Dumond ◽  
Etienne Brachet ◽  
Jérôme Durivault ◽  
Valérie Vial ◽  
Anna K. Puszko ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Dependent Manner ◽  
Cell Renal Cell Carcinoma ◽  
Immunodeficient Mice ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Despite the improvement of relapse-free survival mediated by anti-angiogenic drugs like sunitinib (Sutent ®), or by combinations of anti-angiogenic drugs with immunotherapy, metastatic clear cell Renal Cell Carcinoma (mccRCC) remain incurable. Hence, new relevant treatments are urgently needed. The VEGFs coreceptors, Neuropilins 1, 2 (NRP1, 2) are expressed on several tumor cells including ccRCC. We analysed the role of the VEGFs/NRPs signaling in ccRCC aggressiveness and evaluated the relevance to target this pathway.Methods: We correlated the NRP1, 2 levels to patients’ survival using online available data base. Human and mouse ccRCC cells were knocked-out for the NRP1 and NRP2 genes by a CRISPR/Cas9 method. Their proliferation and migration were evaluated by XTT or impedance tests and by wound closure. Production of VEGFA and VEGFC was evaluated by ELISA. Experimental ccRCC were performed in immuno-competent/deficient mice. The effects of a competitive inhibitor of NRP1, 2, NRPa-308, was tested in vitro and in vivo with the above-mentioned tests and on experimental ccRCC. NRPa-308 docking on both NRPs was performed.Results: Invalidation of the NRP1 and NRP2 genes inhibited cell proliferation and migration and stimulated the expression of VEGFA or VEGFC, respectively. NRPa-308 presented a higher affinity for NRP2 than for NRP1. It decreased cell proliferation and migration more efficiently than sunitinib and the commercially available NRP inhibitor EG00229. NRPa-308 presented a robust inhibition of experimental ccRCC growth in immunocompetent and immunodeficient mice in a reverse dose dependent manner. Such inhibition was associated with a decreased expression of several pro-tumoral factors. Analysis of the TCGA database showed that NRP2, more than NRP1 correlates with tumor aggressiveness only in metastatic patients.Conclusion: Our study strongly suggests that inhibiting NRP is a good therapeutic strategy for mccRCC patients in therapeutic impasses and NRPa-308 represents a relevant hit.

scholarly journals Long non-conding RNA LOXL1-AS1 sponges miR-589-5p to up-regulate CBX5 expression in renal cell carcinoma

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Chunlei Wu ◽  
Jiange Zhang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Function ◽  
Luciferase Reporter ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Renal cell carcinoma (RCC) is a common malignant tumor that seriously endangers people’s health. In recent years, long non-coding RNAs (lncRNAs) have been discovered to play vital roles in diverse cancers, including RCC. LncRNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) has been found to exert carcinogenic functions in several cancers, but its role and mechanism in RCC have not been investigated. Methods: qRT-PCR was utilized for testing RNA expression and Western blot for protein expression in RCC tissues or cells. Then, we assessed cell function by conducting a series of functional experiments, such as 5-ethynyl-2′-deoxyuridine staining, colony formation, flow cytometry, JC-1, Western blot and transwell migration experiments. Following, RNA immunoprecipitation, pull down and luciferase reporter experiments were carried out to explore the regulatory mechanisms of LOXL1-AS1 in RCC. Results: LOXL1-AS1 was highly expressed in RCC tissues and cells. Moreover, knockdown of LOXL1-AS1 hampered RCC cell proliferation and migration. Importantly, miR-589-5p that was lowly expressed and worked as a tumor-inhibitor in RCC was found to bind with LOXL1-AS1. Furthermore, chromobox 5 (CBX5) targeted by miR-589-5p could expedite cell proliferation and migration in RCC. Finally, overexpressed CBX5 or inhibited miR-589-5p reversed the repressive impacts of silenced LOXL1-AS1 on RCC malignant phenotypes. Conclusions: LncRNA LOXL1-AS1 sequestered miR-589-5p to augment CBX5 expression in RCC cells, opening a new way for potential development in RCC treatment.

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