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E2F1‐mediated MNX1‐AS1‐miR‐218‐5p‐SEC61A1 feedback loop contributes to the progression of colon adenocarcinoma
Author(s) -
Ye Yaqun,
Gu Binbin,
Wang Yi,
Shen Sudan,
Huang Wei
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27902
Subject(s) - competing endogenous rna , biology , cancer research , downregulation and upregulation , chromatin immunoprecipitation , e2f1 , microrna , adenocarcinoma , colorectal cancer , antisense rna , long non coding rna , promoter , transcription factor , rna , gene , cancer , gene expression , genetics
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.