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LncRNA EWSAT1 promotes colorectal cancer progression by regulating the miR-330-5p/CPEB4 axis
Chu-Xian Tang1, Dong-Fang Xie2, Xin-Bin Wang2
1Qingdao Medical College of Qingdao University Qingdao 266073, Shandong, China.
None:
Ewing sarcoma-associated transcript 1 (EWSAT1) has been implicated in colorectal cancer (CRC) progression, but its downstream regulatory mechanisms remain unclear. This study aimed to investigate whether EWSAT1 promotes the malignant progression of CRC via the miR-330-5p/CPEB4 axis. The expression levels of EWSAT1, miR-330-5p, and CPEB4 in 30 pairs of CRC tissues and adjacent normal tissues were detected by qRT-PCR. The effects of siRNA-mediated EWSAT1 knockdown on cell proliferation, migration, invasion, and apoptosis were evaluated in HCT-15 and HCT-116 cells. RNA pull-down and dual-luciferase reporter assays were performed to verify the interactions between EWSAT1 and miR-330-5p, as well as between miR-330-5p and the 3'-UTR of CPEB4. Additionally, qRT-PCR, Western blot analysis, and rescue assays (via miR-330-5p inhibition or CPEB4 overexpression) were employed to clarify the functional role of this regulatory axis. The expression levels of EWSAT1 and CPEB4 were increased, while that of miR-330-5p was decreased in CRC tissues compared with adjacent normal tissues. Knockdown of EWSAT1 significantly inhibited the proliferation, migration, and invasion of CRC cells, and promoted their apoptosis. Mechanistically, EWSAT1 could directly bind to miR-330-5p, thereby alleviating the inhibitory effect of miR-330-5p on CPEB4. Inhibition of miR-330-5p or overexpression of CPEB4 could partially reverse the suppression of malignant phenotypes induced by EWSAT1 knockdown. Furthermore, high CPEB4 expression was associated with poorer survival outcomes in CRC patients. In conclusion, EWSAT1 promotes the malignant phenotypes of CRC cells by regulating the miR-330-5p/CPEB4 axis. This molecular axis may provide new insights into the mechanisms of CRC progression and potential targeted interventions.
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