miR-429-CRKL axis regulates clear cell renal cell carcinoma malignant progression through SOS1/MEK/ERK/MMP2/MMP9 pathway
| Autor: | Weibin Sun, Dongting Zhao, Chunmei Guo, Jinxia Wang, Ming-Zhong Sun, Yuxiang Tian, Chengyi Wang, Sixiong Jiang, Qian Li, Lihong Hao, Shuqing Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine MAPK/ERK pathway MMP2 MAP Kinase Signaling System Down-Regulation RM1-950 Biology medicine.disease_cause 03 medical and health sciences Adapter molecule crk 0302 clinical medicine Cell Line Tumor medicine Humans Carcinoma Renal Cell MiR-429-CRKL axis Adaptor Proteins Signal Transducing Pharmacology Oncogene General Medicine Middle Aged Prognosis medicine.disease SOS1/MEK/ERK/MMP2/MMP9 pathway Kidney Neoplasms Up-Regulation CRKL Clear cell renal carcinoma(ccRCC) MicroRNAs Clear cell renal cell carcinoma 030104 developmental biology Matrix Metalloproteinase 9 Gene Knockdown Techniques 030220 oncology & carcinogenesis Cancer cell Tumorigenesis Disease Progression Cancer research Matrix Metalloproteinase 2 Female Therapeutics. Pharmacology SOS1 Protein Carcinogenesis |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 127, Iss, Pp 110215-(2020) |
| ISSN: | 0753-3322 |
| Popis: | The pathogenesis and tumorigenesis of clear cell renal cell carcinoma (ccRCC) remain unclear. The deregulations of miR-429, a member of miR-200 family, and v-crk sarcoma virus CT10 oncogene homologue (avian)-like (CRKL), an adaptor protein of CRK family, are involved in the development, metastasis and prognosis of various cancers. Current study aimed to demonstrate the differential expressions of miR-429 and CRKL with their correlationship and molecular regulation mechanism in ccRCC malignancy. miR-429 and CRKL separately showed suppressing and promoting effects in ccRCC. Lower miR-429 expression and higher CRKL expression were negatively correlated in surgical cancerous tissues by promoting the advance of ccRCC. By binding to the 3'-UTR of CRKL, miR-429 reversely regulated CRKL for its functionalities in ccRCC cells. CRKL knockdown and overexpression separately decreased and increased the in vitro migration and invasion of 786-O cells, which were consistent with the influences of miR-429 overexpression and knockdown on 786-O through respectively downregulating and upregulating CRKL via SOS1/MEK/ERK/MMP2/MMP9 pathway. The enhancements of CRKL expression, migration and invasion abilities and SOS1/MEK/ ERK/MMP2/MMP9 activation induced by TGF-β stimulation in 786-O cells could be antagonized by miR-429 overexpression. Exogenous re-expression of CRKL abrogated miR-429 suppression on the migration and invasion of 786-O cells. Collectively, miR-429 deficiency negatively correlated with CRKL overexpression promoted the aggressiveness of cancer cells and advanced the clinical progression of ccRCC patients. miR-429-CRKL axial regulation provides new clues to the fundamental research, diagnosis and treatment of ccRCC. |
| Databáze: | OpenAIRE |
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