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Published on: May 21, 2019
Targeting LncRNA EPIC1 to inhibit human colon cancer cell progression
Qiong Wu1, Jue Wei1, Chen Zhao1
1Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Long non-coding RNA EPIC1 (Lnc-EPIC1) binds MYC protein, which is essential for MYC function and expression of MYC target genes. The current study tested its expression and potential functions in human colon cancer cells. We show that Lnc-EPIC1 expression is elevated in human colon cancer tissues and primary human colon cancer cells. Whereas its expression is relatively low in normal colon tissues and colon epithelial cells. In the primary human colon cancer cells, Lnc-EPIC1 siRNA largely inhibited cancer cell growth, proliferation, migration and invasion. Further, Lnc-EPIC1 silencing induced significant apoptosis activation in colon cancer cells. Conversely, ectopic overexpression of Lnc-EPIC1 augmented colon cancer cell growth, proliferation, migration and invasion. RNA-immunoprecipitation and RNA pull-down results confirmed that Lnc-EPIC1 directly binds MYC protein in colon cancer cells. MYC target proteins, including cyclin A, cyclin D and CDK9, were downregulated with Lnc-EPIC1 silencing, but upregulated after Lnc-EPIC1 overexpression in colon cancer cells. Further Lnc-EPIC1 silencing or overexpression failed to alter functions of MYC-knockout colon cancer cells. Collectively, overexpressed Lnc-EPIC1 is important for the progression of human colon cancer cells.
Insights
Long non-coding RNA EPIC1 (Lnc-EPIC1) promotes human colon cancer progression by binding to MYC. Silencing Lnc-EPIC1 inhibits cancer cell growth, migration, and invasion, while its overexpression enhances these processes.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) play crucial roles in cellular processes.
- MYC protein is a key regulator of cell growth and proliferation, and its dysregulation is common in cancer.
- The specific role of Lnc-EPIC1 in colon cancer has not been fully elucidated.
Purpose of the Study:
- To investigate the expression levels of Lnc-EPIC1 in human colon cancer.
- To determine the functional role of Lnc-EPIC1 in colon cancer cell proliferation, migration, invasion, and apoptosis.
- To elucidate the interaction between Lnc-EPIC1 and MYC in colon cancer cells.
Main Methods:
- Quantitative real-time PCR to assess Lnc-EPIC1 expression in colon cancer tissues and cells.
- siRNA-mediated knockdown and ectopic overexpression of Lnc-EPIC1 in colon cancer cell lines.
- Cell proliferation, migration, invasion, and apoptosis assays.
- RNA-immunoprecipitation and RNA pull-down assays to confirm direct binding of Lnc-EPIC1 to MYC.
- Western blotting to analyze the expression of MYC target genes.
Main Results:
- Lnc-EPIC1 expression was significantly elevated in human colon cancer tissues and cells compared to normal tissues and cells.
- Lnc-EPIC1 silencing inhibited colon cancer cell growth, proliferation, migration, and invasion, and induced apoptosis.
- Lnc-EPIC1 overexpression promoted colon cancer cell growth, proliferation, migration, and invasion.
- Lnc-EPIC1 directly binds to MYC protein in colon cancer cells.
- Silencing or overexpression of Lnc-EPIC1 altered the expression of MYC target proteins (cyclin A, cyclin D, CDK9) in a manner consistent with MYC regulation.
- Functional alterations of Lnc-EPIC1 were dependent on MYC expression, as Lnc-EPIC1 manipulation had no effect in MYC-knockout cells.
Conclusions:
- Overexpressed Lnc-EPIC1 is a critical driver of human colon cancer progression.
- Lnc-EPIC1 exerts its oncogenic functions by directly interacting with MYC, influencing MYC target gene expression and downstream cellular processes.
- Lnc-EPIC1 represents a potential therapeutic target for colon cancer treatment.
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