期刊
MOLECULAR THERAPY-ONCOLYTICS
卷 20, 期 -, 页码 607-624出版社
CELL PRESS
DOI: 10.1016/j.omto.2021.01.003
关键词
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资金
- Science and Technology Department of Jilin Province [20170520011JH]
- Youth Mainstay Program of the First Hospital of Jilin University
The study found that DLGAP1-AS1 plays a crucial role in the progression of colorectal carcinoma and 5-FU resistance through the miR-149-5p/TGFB2 regulatory axis. Silencing DLGAP1-AS1 inhibited cell proliferation and invasiveness, while enhancing the sensitivity of CRC cells to 5-FU chemotherapy.
Colorectal carcinoma (CRC) ranks as the third most common malignancy. Long non-coding RNA DLGAP1-AS1 was reported to be dysregulated and to play a pivotal role in hepatocellular carcinoma (HCC). This work aims to analyze the functions and molecular basis of DLGAP1-AS1 in CRC progression and 5-fluorouracil resistance. Cell Counting Kit-8 (CCK-8) assay, Transwell assay, flow cytometry, and western blot were utilized to measure the CRC cell activity, invasiveness, and apoptosis. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assay were adopted to verify the direct mutual action between DLGAP1-AS1 and miR-149-5p. The effect of DLGAP1-AS1 knockdown on tumor growth and chemosensitivity of 5-fluorouracil (5-FU) were investigated in the mouse CRC xenograft models. Functional assays showed that silencing DLGAP1-AS1 expression remarkably inhibited cell proliferation and aggressiveness ability and enhanced apoptosis rate and cell chemosensitivity to 5-FU. In addition, miR-149-5p was identified as a tumor suppressor and a direct downstream target of DLGAP1-AS1 in CRC. Furthermore, miR-149-5p was confirmed to directly bind to TGFB2 and DLGAP1-AS1 could regulate the expression of TGFB2 signaling pathway via miR-149-5p in CRC. These new findings indicate that DLGAP1-AS1 knockdown inhibited the progression of CRC and enhanced the 5-FU sensitivity of CRC cells through miR-149-5p/TGFB2 regulatory axis, suggesting that DLGAP1-AS1 may be a promising therapeutic target for CRC.
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