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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
MicroRNA-455 suppresses the oncogenic function of HDAC2 in human colorectal cancer
1Department of Gastroenterology, Huangdao Division, The Affiliated Hospital of Qingdao University, Qingdao, China.
Abstract:
Colorectal cancer (CRC) is the fourth leading cause of cancer-induced mortality. Histone deacetylase 2 (HDAC2) is involved in prognosis and therapy of CRC. This study aimed to explore novel therapeutic targets for CRC. The alteration of HDAC2 expression in CRC tissues was estimated by qRT-PCR. After lentivirus transfection, HDAC2 knockdown was confirmed by western blot analysis. The effect of HDAC2 knockdown on cell proliferation was then assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Screened by TargetScan, microRNA (miR)-455 was predicted to bind to 3'UTR of HDAC2 and the prediction was verified by luciferase assay. Finally, cells were transfected, respectively, with miR-455 mimics or miR-455 negative control (miR-NC) and the expression of HDAC2, cell proliferation and apoptosis of transfected cells were respectively evaluated by western blot analysis, MTT assay and flow cytometry. Results showed that the HDAC2 expression was up-regulated in CRC tissues (P<0.05). HDAC2 knockdown significantly decreased cell viability at day 3 (P<0.05), day 4 (P<0.01), and day 5 (P<0.001) after infection. Then, miR-455 was verified to directly target HDAC2, resulting in a significant difference in luciferase activity (P<0.01). Moreover, miR-455 decreased the expression of HDAC2 (P<0.01). miR-455 remarkably decreased cell viability at day 3 (P<0.05), day 4 (P<0.01), and day 5 (P<0.001) after transfection while inducing cell apoptosis (P<0.001). In conclusion, miR-455 inhibited cell proliferation while inducing cell apoptosis by targeting HDAC2 in CRC cells.
Insights
MicroRNA-455 targets Histone deacetylase 2 (HDAC2) to inhibit colorectal cancer (CRC) cell proliferation and induce apoptosis. This study identifies a novel therapeutic strategy for CRC by targeting the miR-455/HDAC2 pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) is a major cause of cancer mortality.
- Histone deacetylase 2 (HDAC2) plays a role in CRC prognosis and therapy.
- Identifying novel therapeutic targets is crucial for effective CRC treatment.
Purpose of the Study:
- To investigate the role of HDAC2 in colorectal cancer.
- To explore microRNA-455 (miR-455) as a potential therapeutic agent targeting HDAC2 in CRC.
- To elucidate the mechanism by which miR-455 affects CRC cell behavior.
Main Methods:
- HDAC2 expression was quantified in CRC tissues using qRT-PCR.
- HDAC2 knockdown was achieved via lentivirus transfection and confirmed by western blot.
- Cell proliferation was assessed using MTT assays.
- The interaction between miR-455 and HDAC2 was validated using luciferase assays.
- miR-455 mimics were transfected to evaluate effects on HDAC2 expression, cell proliferation, and apoptosis (flow cytometry).
Main Results:
- HDAC2 expression was significantly upregulated in CRC tissues.
- HDAC2 knockdown markedly reduced CRC cell viability.
- miR-455 was confirmed to directly target HDAC2.
- miR-455 transfection decreased HDAC2 expression, inhibited cell proliferation, and induced significant apoptosis in CRC cells.
Conclusions:
- miR-455 acts as a tumor suppressor in colorectal cancer by targeting HDAC2.
- The miR-455/HDAC2 axis represents a promising therapeutic target for CRC treatment.
- Targeting miR-455 could offer a novel strategy to inhibit CRC progression and induce cancer cell death.
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