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miR‑29a suppresses the growth and metastasis of hepatocellular carcinoma through IFITM3
Yiming Liang1, Enliang Li2, Jiaqi Min1
1Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Abstract:
The interferon-induced transmembrane protein 3 (IFITM3, also called 1‑8U) gene represents dysregulated expression in various tumors and is involved in tumorigenesis and progression. However, the role of IFITM3 and its underlying mechanism in hepatocellular carcinoma (HCC) are still far from elucidated. MicroRNAs (miRNAs), a class of endogenous (approximately 22 nucleotides) small noncoding RNAs, can post‑transcriptionally regulate gene expression by repressing protein translation or silencing the expression of target genes that play critical roles in various cancers. miR‑29a was identified as being aberrantly expressed in a significant proportion of HCC. However, the correlation between IFITM3 and miR‑29a has not been reported to date. In this study, we investigated the expression of IFITM3 in HCC and its effect on the biological behavior of HCC cells as well as the association between IFITM3 and miR‑29a. We determined that IFITM3 was upregulated and miR‑29a downregulated in HCC tissues and that they were associated with HCC tumor size, tumor multifocal, and venous invasion. The expression of IFITM3 in HCC tissues was negatively correlated with miR‑29a expression. Additionally, IFITM3 overexpression and miR‑29a nonoverexpression were related to poor prognosis of HCC patients. Knockdown of IFITM3 inhibited migration, invasion, proliferation and promoted apoptosis of HCC cells, which are consistent with the effects of upregulated miR‑29a. Additionally, after upregulation of IFITM3, the invasion, migration and proliferation abilities of HL‑7702 cells were increased, but the apoptosis rate was decreased. Furthermore, using a Dual‑Luciferase reporter gene assay, we identified IFITM3 as a new functional target gene of miR‑29a. In conclusion, our findings demonstrated that the migration, invasion, proliferation and apoptosis features of HCC cells could be regulated by miR‑29a via IFITM3. Thus, the present study indicated that miR‑29a and IFITM3 play critical roles in the development and progression of HCC, revealing that miR‑29a and IFITM3 may be novel potential therapeutic targets for patients with HCC.
Insights
Interferon-induced transmembrane protein 3 (IFITM3) is upregulated and miR-29a is downregulated in hepatocellular carcinoma (HCC), promoting tumor progression. Targeting this miR-29a/IFITM3 axis offers potential new therapies for HCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Interferon-induced transmembrane protein 3 (IFITM3) is implicated in various cancers, but its role in hepatocellular carcinoma (HCC) remains unclear.
- MicroRNAs (miRNAs) regulate gene expression and are critical in cancer development; miR-29a is aberrantly expressed in HCC.
- The relationship between IFITM3 and miR-29a in HCC has not been previously reported.
Purpose of the Study:
- To investigate the expression of IFITM3 and miR-29a in HCC tissues.
- To explore the correlation between IFITM3 and miR-29a and their impact on HCC biological behavior and patient prognosis.
- To elucidate the underlying molecular mechanism involving IFITM3 and miR-29a in HCC progression.
Main Methods:
- Quantitative analysis of IFITM3 and miR-29a expression in HCC tissues.
- In vitro experiments involving IFITM3 knockdown and overexpression in HCC cell lines.
- Dual-luciferase reporter gene assay to confirm the direct targeting of IFITM3 by miR-29a.
Main Results:
- IFITM3 was upregulated and miR-29a downregulated in HCC tissues, correlating with tumor size, multifocality, and venous invasion.
- IFITM3 expression was negatively correlated with miR-29a expression; both were associated with poor HCC prognosis.
- IFITM3 knockdown inhibited HCC cell migration, invasion, and proliferation while promoting apoptosis, mirroring the effects of miR-29a upregulation. Conversely, IFITM3 overexpression in normal cells increased invasion, migration, and proliferation while decreasing apoptosis.
- IFITM3 was identified as a direct target gene of miR-29a.
Conclusions:
- The miR-29a/IFITM3 axis plays a crucial role in regulating the migration, invasion, proliferation, and apoptosis of HCC cells.
- Aberrant expression of miR-29a and IFITM3 is linked to HCC development and progression.
- miR-29a and IFITM3 represent potential novel therapeutic targets for hepatocellular carcinoma.
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