E2F1-mediated MNX1-AS1-miR-218-5p-SEC61A1 feedback loop contributes to the progression of colon adenocarcinoma.

Abstract

The long noncoding RNA MNX1-AS1 has been reported to facilitate the progression of glioblastoma and ovarian cancer. Nevertheless, the biological roles and underlying mechanisms of MNX1-AS1 in colon adenocarcinoma have not been studied until now. In the current study, MNX1-AS1 was upregulated in colon adenocarcinoma. JASPAR prediction tool showed that E2F1 could bind to the promoter region of MNX1-AS1. The chromatin immunoprecipitation assay and luciferase reporter assay were used to verify the interactions between MNX1-AS1 and E2F1. Then functional assays revealed that downregulation of MNX1-AS1 decreased cell proliferation, migration, and invasion in colon adenocarcinoma, but upregulation of E2F1 reversed the effects. Moreover, subcellular fractionation assay manifested that MNX1-AS1 was enriched in the cytoplasm of colon adenocarcinoma cells, thus we speculated whether MNX1-AS1 could function as a competing endogenous RNA (ceRNA) to play roles in colon adenocarcinoma. Bioinformatics analysis and luciferase reporter assay indicated that MNX1-AS1 could sponge microRNA-218-5p (miR-218-5p). Furthermore, we discovered that SEC61A1 was downstream target of miR-218-5p, and MNX1-AS1 acted as a ceRNA to upregulate the expression of SEC61A1 through sponging miR-218-5p. Finally, rescue assays confirmed that MNX1-AS1 facilitated the progression of colon adenocarcinoma through regulating miR-218-5p/SEC61A1 axis. Taken together, we concluded that E2F1-mediated MNX1-AS1-miR-218-5p-SEC61A1 feedback loop contributed to the progression of colon adenocarcinoma.

• Authors: Yaqun Ye, Binbin Gu, Yi Wang, Sudan Shen, Wei Huang
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 120 Issue 4 Pg. 6145-6153 (04 2019) ISSN: 1097-4644 [Electronic] United States
• PMID: 30362161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• E2F1 Transcription Factor
• E2F1 protein, human
• Homeodomain Proteins
• MIRN218 microRNA, human
• MNX1 protein, human
• MicroRNAs
• RNA, Long Noncoding
• SEC Translocation Channels
• SEC61A1 protein, human
• Transcription Factors

Topics

• Adenocarcinoma (genetics, metabolism, pathology)
• Blotting, Western
• Cell Line, Tumor
• Cell Movement (genetics, physiology)
• Cell Proliferation (genetics, physiology)
• Colonic Neoplasms (genetics, metabolism, pathology)
• Disease Progression
• E2F1 Transcription Factor (genetics, metabolism)
• Gene Expression Regulation, Neoplastic (genetics, physiology)
• HT29 Cells
• Homeodomain Proteins (genetics, metabolism)
• Humans
• In Vitro Techniques
• MicroRNAs (genetics, metabolism)
• RNA, Long Noncoding (genetics, metabolism)
• SEC Translocation Channels (genetics, metabolism)
• Transcription Factors (genetics, metabolism)