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LncRNA ELFN1-AS1 promotes colon cancer occurrence and progression by regulating the miR-191-5p/ZBTB34 axis
Yue Jiang1, Yanmei Hou2, Yongjun Du2
1School of Clinical Medicine, Chengdu University of TCM, Chengdu, China.
Background:
Colon cancer (CC) is the fourth most common cancer worldwide and a major cause of cancer-related deaths. The long non-coding RNA ELFN1 antisense RNA 1 (ELFN1-AS1) has been reported to be a cancer driver in many human malignancies. The aim of this study is to investigate the function and mechanism of ELFN1-AS1 in CC.
Methods:
The expression of ELFN1-AS1 in CC cells was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK8) assay, wound healing assay and invasion assay were used to detect the effects of ELFN1-AS1 and miR-191-5p on the proliferation and metastasis of CC cells. StarBase database and dual luciferase gene assay were used to detect the interaction between ELFN1-AS1, miR-191-5p and ZBTB34. The expression of ZBTB34 in CC cells was detected by Western blot. The subcutaneous xenograft experiment in nude mice was conducted to investigate the in vivo effects of ELFN1-AS1 and miR-191-5p on tumor growth. Data analysis platforms such as The Cancer Genome Atlas (TCGA) database, Gene Expression Profiling Interactive Analysis (GEPIA), and cBio Cancer Genomics Portal (cBioPortal) were employed to analyze the correlation between ELFN1-AS1 and the staging and grading of CC. Additionally, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis platform were utilized for co-expression protein network analysis and functional enrichment analysis of the downstream target protein ZBTB34 of miR-191-5p.
Results:
The expression of ELFN1-AS1 in CC tumor tissues was significantly higher than that in adjacent non-tumor tissues. High expression of ELFN1-AS1 was negatively correlated with overall survival in patients with CC and positively associated with disease progression. The expression of ELFN1-AS1 significantly promotes the proliferation, migration, and invasion capabilities of CC cells. miR-191-5p is the target gene of ELFN1-AS1, and overexpression of miR-191-5p can impair the proliferation and metastasis of CC cells. Mechanistically, we found that ELFN1-AS1 functions as a competing endogenous RNA (ceRNA) to down-regulate miR-191-5p expression, thereby increasing the expression of ZBTB34, a downstream gene in this regulatory axis.
Conclusions:
ELFN1-AS1 is involved in the occurrence and development of CC by regulating the miR-191-5p/ ZBTB34 axis. Therefore, targeting this axis may be a promising intervention to prevent CC progression.
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