期刊
BIOENGINEERED
卷 13, 期 3, 页码 5113-5125出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/21655979.2022.2036905
关键词
Colorectal cancer; hsa_circ_0068464; miR-383; Wnt/beta-catenin pathway
资金
- Improvement Project of Young and middle-aged Teachers in Guangxi Colleges and Universities [2019KY0156]
- Health and Family Planning Commission of Guangxi Zhuang Autonomous Region [Z20190002]
- Natural Science Foundation of Guangxi Province [2019GXNSFBA185003, 2018GXNSFBA281113]
- Scientific Research and Technology Development Project of Liuzhou City [2017BH20306]
This study aimed to investigate the influence and mechanism of circular RNA hsa_circ_0068464 (circ_0068464) on the development of colorectal cancer (CRC). The study found that circ_0068464 was abnormally up-regulated in CRC cells and tissues, and its knockdown inhibited CRC cell migration and proliferation while promoting apoptosis. The mechanism involved the regulation of Wnt/beta-catenin pathway activation through targeting miR-383. This study provides new insights into the molecular mechanisms underlying the occurrence and development of CRC.
This study was to clarify the influence and mechanism of circular RNA hsa_circ_0068464 (circ_0068464) on the development of colorectal cancer (CRC). First, we combined bioinformatics analysis and the high-throughput sequencing to determine the expression profile of circRNAs in CRC dataset, and screened out the differentially expressed circ_0068464. Subsequently, qRT-PCR was utilized to measure circ_0068464 expression in CRC and normal cancer-adjacent tissues, CRC cell lines (SW480, SW620, HT29, LS174T and HCT116) and human fetal intestinal epithelial cell (FHC). The results revealed that circ_0068464 was abnormally up-regulated in CRC cells and tissues. Knockdown of circ_0068464 could inhibit CRC cell migration and proliferation and promoted apoptosis while suppressing the expression of Wnt/beta-catenin pathway-related proteins (beta-catenin, cyclin D1, C-myc and LEF-1). In addition, tumorigenic assays in nude mice confirmed that circ_0068464 downregulation significantly inhibited tumor growth and lung metastasis. Further, the binding interaction between circ_0068464 and microRNA-383 (miR-383) was verified by dual-luciferase assay and RNA immunoprecipitation assay. And miR-383 was significantly down-regulated in CRC tissues and cells. Interfering with miR-383 expression reversed the inhibitory effect of circ_0068464 knockdown on CRC cells. In conclusion, circ_0068464 targets miR-383 to regulate Wnt/beta-catenin pathway activation, thereby promoting the development of CRC. [GRAPHICS] .
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