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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MiR-454 prompts cell proliferation of human colorectal cancer cells by repressing CYLD expression
Hong-Liang Liang1, Ai-Ping Hu, Sen-Lin Li
1Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, China
Abstract:
Previous studies have shown that miR-454 plays an important role in a variety of biological processes in various human cancer cells. However, the underlying mechanisms of this microRNA in colorectal cancer (CRC) cells remain largely unknown. In the present study, we investigated the miR-454 role in CRC cell proliferation. We found that miR-454 expression is markedly upregulated in CRC tissues and CRC cells compared with the matched tumor adjacent tissues and the FHC normal colonic cell line. Ectopic expression of miR-454 promoted the proliferation and anchorage-independent growth of CRC cells, whereas inhibition of miR-454 reduced this effect. Bioinformatics analysis further revealed cylindromatosis (CYLD), a putative tumor suppressor as a potential target of miR-454. Data from luciferase reporter assays showed that miR-454 directly binds to the 3'-untranslated region (3'-UTR) of CYLD mRNA and repressed expression at both transcriptional and translational levels. In functional assays, CYLD-silenced in miR-454-in-transfected SW480 cells have positive effect to promote cell proliferation, suggesting that direct CYLD downregulation is required for miR-454-induced CRC cell proliferation. In sum, our data provide compelling evidence that miR-454 functions as an onco-miRNA, playing a crucial role in the promoting cell proliferation in CRC, and its oncogenic effect is mediated chiefly through direct suppression of CYLD expression.
Insights
MicroRNA-454 (miR-454) promotes colorectal cancer (CRC) cell proliferation by downregulating the tumor suppressor CYLD. This finding reveals miR-454 as a potential therapeutic target in CRC treatment.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression implicated in various cancers.
- The specific role and mechanism of miR-454 in colorectal cancer (CRC) proliferation remain largely unelucidated.
- Understanding miRNA functions is crucial for developing targeted cancer therapies.
Purpose of the Study:
- To investigate the role of miR-454 in colorectal cancer (CRC) cell proliferation.
- To identify the molecular targets and mechanisms underlying miR-454's function in CRC.
- To explore the potential of miR-454 as a therapeutic target in CRC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to assess miR-454 expression levels in CRC tissues and cell lines.
- Cell proliferation assays (e.g., MTT, colony formation) to evaluate the impact of miR-454 modulation on CRC cell growth.
- Bioinformatics analysis to predict potential miR-454 targets.
- Luciferase reporter assays to validate direct binding of miR-454 to the 3'-untranslated region (3'-UTR) of target mRNA.
- Western blotting and gene silencing techniques to assess protein expression and functional consequences.
Main Results:
- miR-454 expression was significantly upregulated in CRC tissues and cells compared to normal tissues and cell lines.
- Overexpression of miR-454 enhanced CRC cell proliferation and anchorage-independent growth.
- Inhibition of miR-454 suppressed CRC cell proliferation.
- Cylindromatosis (CYLD), a tumor suppressor, was identified as a direct target of miR-454.
- miR-454 directly binds to the 3'-UTR of CYLD mRNA, repressing its expression at both transcriptional and translational levels.
- Downregulation of CYLD by miR-454 was essential for promoting CRC cell proliferation.
Conclusions:
- miR-454 acts as an onco-microRNA in colorectal cancer (CRC).
- miR-454 promotes CRC cell proliferation primarily by directly suppressing the expression of the tumor suppressor CYLD.
- Targeting miR-454 or its downstream effects on CYLD may offer a novel therapeutic strategy for CRC.
