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Published on: September 12, 2019
Let-7c-5p down-regulates immune-related CDCA8 to inhibit hepatocellular carcinoma
Wanjin Chen1,2, Haibo Wang1, Yuanlong Shen3
1Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, China.
Objective:
The aim of this study is to investigate the effect of let-7c-5p on the malignant behaviors of hepatocellular carcinoma (HCC) and its specific molecular pathway.
Methods:
Differential expression and survival analysis of let-7c-5p were obtained from The Cancer Genome Atlas database, and then its expression level was preliminarily verified through qPCR. The effect of let-7c-5p on the malignant phenotype of HCC cells was subsequently evaluated using CCK-8, transwell, wound healing, and flow cytometry assays. Downstream mRNA regulated by let-7c-5p was identified and confirmed by ENCORI database, dual-luciferase reporter, and western blot assays. The immunocorrelation of genes was evaluated by Xiantao tool, and TIMER and TISIDB databases.
Results:
The expression level of let-7c-5p in HCC was obviously reduced, which was found to be closely associated with the short survival time of HCC patients. Cell phenotypic experiments showed that let-7c-5p inhibited proliferation, invasion, and migration and promoted apoptosis of HCC cells. Dual-luciferase reporter and western blot analysis demonstrated that CDCA8 is a downstream mRNA of let-7c-5p and is negatively regulated by it. Rescue experiment revealed that CDCA8 reversed the effect of let-7c-5p on the malignant phenotype of HCC cells. Furthermore, analysis of the public database revealed that CDCA8 is related to some immune cells and immunomodulators, and that it may participate in the regulation of some immune pathways and immune functions.
Conclusion:
Let-7c-5p has been proved to suppress HCC by down-regulating immune-related CDCA8, which will help understand the pathogenesis of HCC and develop drugs for its treatment.
Insights
Let-7c-5p suppresses hepatocellular carcinoma (HCC) by reducing CDCA8, inhibiting cancer growth and improving patient survival. This finding offers new therapeutic strategies for HCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Hepatocellular carcinoma (HCC) is a major global health concern with limited effective treatments.
- Understanding the molecular mechanisms underlying HCC progression is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of let-7c-5p in hepatocellular carcinoma (HCC) progression.
- To elucidate the specific molecular pathway through which let-7c-5p exerts its effects.
- To explore the potential of let-7c-5p as a therapeutic target for HCC.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database for differential expression and survival analysis of let-7c-5p.
- Validated let-7c-5p expression using quantitative real-time PCR (qPCR).
- Assessed the impact of let-7c-5p on HCC cell phenotypes (proliferation, invasion, migration, apoptosis) via CCK-8, Transwell, wound healing, and flow cytometry assays.
- Identified and confirmed CDCA8 as a direct downstream target of let-7c-5p using ENCORI, dual-luciferase reporter assays, and Western blot.
- Evaluated the immunocorrelation of CDCA8 using Xiantao, TIMER, and TISIDB databases.
Main Results:
- Let-7c-5p expression was significantly downregulated in HCC tissues and correlated with poor patient survival.
- Overexpression of let-7c-5p inhibited HCC cell proliferation, invasion, and migration, while promoting apoptosis.
- CDCA8 was identified as a direct, negatively regulated target of let-7c-5p.
- Knockdown of CDCA8 reversed the inhibitory effects of let-7c-5p on HCC cell malignancy, confirming its role in the pathway.
- CDCA8 showed associations with immune cells and immunomodulators, suggesting its involvement in immune regulation within the HCC microenvironment.
Conclusions:
- Let-7c-5p acts as a tumor suppressor in HCC by downregulating the expression of CDCA8.
- This let-7c-5p/CDCA8 axis provides insights into HCC pathogenesis and presents a potential therapeutic target for HCC treatment.
- Targeting the let-7c-5p/CDCA8 pathway may offer a novel strategy for improving HCC treatment outcomes.
