Long Noncoding RNA DLX6-AS1 Regulates the Growth and Aggressiveness of Colorectal Cancer Cells Via Mediating the miR-26a/EZH2 Axis.

Abstract

Objective: To understand the regulation of long noncoding RNA DLX6-AS1-mediated miR-26a/EZH2 axis in the growth of colorectal cancer (CRC) cells. Methods: The expression of DLX6-AS1, miR-26a, and EZH2 was detected in CRC tissues by quantitative reverse transcription-polymerase chain reaction. The CRC HT-29 cell line was selected for transfection and subjected to observe the growth by MTT and colony formation assays, cell cycle by flow cytometry, and migration and invasion by wound healing and Transwell assays, respectively. Finally, the expression of cycle- and metastasis-related proteins was detected by Western blotting. Results: DLX6-AS1 and EZH2 were increased, with a decreased miR-26a in CRC tissues, showing significant negative correlations between DLX6-AS1 and miR-26a, and between miR-26a and EZH2. CRC patients at advanced stage or with lymphatic metastasis had higher DLX6-AS1 expression. Dual-luciferase reporter gene assay uncovered the targeting correlations between DLX6-AS1 and miR-26a, or miR-26a and EZH2. After transfection of DLX6-AS1 siRNA or EZH2 siRNA, the growth and metastasis of CRC cells were suppressed, arresting the cells in G0/G1 phase, with a magnificent reduction in the ratio of cells in S phase or G2/M phase; meanwhile, Cyclin D1, Vimentin, and MMP9 expressions decreased evidently, whereas E-cadherin expression was upregulated. Changes above were fully reversed after transfection of miR-26a inhibitor, whereas si-EZH2 transfection abolished the positive role of miR-26a inhibitor on growth of CRC cells. Conclusion: Silencing DLX6-AS1 may block the malignant features of CRC cells by inhibiting the expression of EZH2 through upregulation of miR-26a. Thus, it is critical to the development and progression of CRC.

• Authors: Wei-Qi Kong, Jian-Jing Liang, Jing Du, Zhen-Xiong Ye, Ping Gao, Yu-Long Liang
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 36 Issue 9 Pg. 753-764 (Nov 2021) ISSN: 1557-8852 [Electronic] United States
• PMID: 32379493 (Publication Type: Journal Article)

Chemical References

• Cell Cycle Proteins
• DLX6 protein, human
• Homeodomain Proteins
• MIRN26A microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• EZH2 protein, human
• Enhancer of Zeste Homolog 2 Protein

Topics

• Cell Cycle Checkpoints (genetics)
• Cell Cycle Proteins (analysis)
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Enhancer of Zeste Homolog 2 Protein (antagonists & inhibitors, genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Gene Transfer Techniques
• HT29 Cells
• Homeodomain Proteins (genetics, metabolism)
• Humans
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• RNA, Long Noncoding
• Signal Transduction
• Up-Regulation