The Roles of Beclin 1 Expression in Gastric Cancer: A Marker for Carcinogenesis, Aggressive Behaviors and Favorable Prognosis, and a Target of Gene Therapy
| Autor: | Hang Xue, En-Hong Zhao, Hua-Mao Jiang, Hua-Chuan Zheng, Shuang Zhao, Chang-Lai Hao |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Protein degradation medicine.disease_cause lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine medicine Original Research business.industry gastric cancer Autophagy Cancer BECN1 medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Beclin 1 gene therapy aggressive behaviors Gastric chief cell 030104 developmental biology Oncology Gastric pits 030220 oncology & carcinogenesis Cancer cell Cancer research prognosis Carcinogenesis business carcinogenesis |
| Zdroj: | Frontiers in Oncology Frontiers in Oncology, Vol 10 (2020) |
| ISSN: | 2234-943X |
| DOI: | 10.3389/fonc.2020.613679 |
| Popis: | Beclin 1 is encoded by Becn1, and plays a role in tumorigenesis, neurodegeneration, apoptosis and autophagy. Here, the aggressive phenotypes and relevant proteins were examined after Beclin 1 expression was altered in gastric cancer cells. We also observed the effects of Beclin 1 on gastric carcinogenesis using Becn1 knockout mice. Finally, clinicopathological significances of Beclin 1 expression were analyzed using meta- and bioinformatics analyses. Becn1 overexpression was found to inhibit proliferation, glucose metabolism, migration and invasion of gastric cancer cells, whereas its knockdown caused the opposite effects. Beclin 1 suppressed the tumor growth by decreasing proliferation and increasing apoptosis. The heterozygous abrogation of Becn1 in gastric pit, parietal and chief cells could not cause any epithelial lesion. Beclin 1-mediated chemoresistance was closely linked to the autophagy, Bax underexpression, and the overexpression of Bcl-2, LRP1, MDR1, and ING5. Bioinformatics analysis showed higher Becn1 mRNA expression in intestinal- than diffuse-type carcinomas (PPBecn1 hyperexpression was positively associated with both overall and progression-free survival rates of the cancer patients (PPBecn1-related signal pathways in gastric cancer included prostate, lung, renal, colorectal, endometrial and thyroid cancers, glioma, and leukemia, the metabolism of amino acid, lipid and sugar, and some signal pathways of insulin, MAPK, TRL, VEGF, JAK-STAT, chemokine, p53, lysosome, peroxidome and ubiquitin-mediated protein degradation (P |
| Databáze: | OpenAIRE |
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