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[miR-29a-3p Targets Hepatoma-Derived Growth Factor to Inhibit the Proliferation and Promote the Apoptosis of E6-1
Jian Zhou1, Chun-Lan Huang2, Heng-Wei Liu1
1Department of Hematology, The Third People's Hospital of Chengdu, Chengdu 610031, Sichuan Province, China.
Objective:
To investigate the regulatory effect of miRNA-29a-3p (miR-29a-3p ) on hepatoma-derived growth factor (HDGF), and its influences on the proliferation and apoptosis of acute lymphoblastic leukemia (ALL) cell line E6-1.
Methods:
Thirty-five patients with ALL treated in our hospital from January 2017 to January 2019 were selected as research objects, and 35 adults who underwent physical examination in the same period were selected as healthy control group. The miR-29a-3p overexpression vector, miR-29a-3p inhibitory expression vector, and miR-29a-3p and HDGF co-overexpression vector were transfected into E6-1 cells. The expression levels of miR-29a-3p and HDGF mRNA were detected by RT-qPCR. The expression of protein was detected by Western blot. The targeting relationship between miR-29a-3p and HDGF was detected by dual luciferase reporter assay. The cell proliferation was detected by CCK-8 method, while apoptosis detected by flow cytometry.
Results:
Compared with healthy control group, HDGF was highly expressed in serum of patients with ALL and leukemia cells HuT 78, E6-1, CCRF-CEM, while miR-29a-3p was low expressed (P<0.05). After overexpression of miR-29a-3p , the expression levels of CyclinD1 and Bcl-2 in leukemia cells E6-1 were significantly reduced, while the expression levels of p21 and Bax were significantly increased (P<0.05). The activity of E6-1 cells was also significantly reduced, while the apoptosis rate of E6-1 cells was significantly increased (P<0.05). miR-29a-3p could target and regulate the expression of HDGF, while overexpression of HDGF reversed the inhibitory effect of miR-29a-3p overexpression on the proliferation and promotion effect on the apoptosis of leukemia cells E6-1.
Conclusion:
Overexpression of miR-29a-3p can inhibit the proliferation and promote the apoptosis of ALL cells E6-1, and its mechanism may be related to the regulation of HDGF expression.
Insights
MicroRNA-29a-3p (miR-29a-3p) inhibits acute lymphoblastic leukemia (ALL) cell proliferation and promotes apoptosis by targeting hepatoma-derived growth factor (HDGF). Upregulating miR-29a-3p offers a potential therapeutic strategy for ALL.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Context:
- Acute lymphoblastic leukemia (ALL) is a hematological malignancy with complex regulatory mechanisms.
- Hepatoma-derived growth factor (HDGF) has been implicated in various cancers, including leukemia.
- MicroRNAs (miRNAs) play crucial roles in post-transcriptional gene regulation and are often dysregulated in cancer.
Purpose:
- To investigate the regulatory role of miR-29a-3p in ALL.
- To determine the relationship between miR-29a-3p and HDGF in ALL cells.
- To assess the impact of miR-29a-3p on the proliferation and apoptosis of the ALL cell line E6-1.
Summary:
- HDGF expression was elevated, while miR-29a-3p was downregulated in ALL patients and cell lines compared to healthy controls.
- Overexpression of miR-29a-3p in E6-1 cells led to decreased proliferation and increased apoptosis, evidenced by changes in CyclinD1, Bcl-2, p21, and Bax.
- Dual luciferase reporter assays confirmed that miR-29a-3p directly targets HDGF. Overexpression of HDGF counteracted the effects of miR-29a-3p.
Impact:
- This study elucidates a novel regulatory pathway involving miR-29a-3p and HDGF in ALL.
- Findings suggest that miR-29a-3p acts as a tumor suppressor in ALL by inhibiting cell proliferation and inducing apoptosis.
- miR-29a-3p represents a potential therapeutic target for ALL treatment.
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