Tumor-suppressor role of miR-139-5p in endometrial cancer
JinHui Liu1, ChunYu Li2, Yi Jiang1
11Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 Jiangsu China.
Background:
Endometrial cancer (EC) is the fourth most common malignancy of the female genital tract worldwide. MicroRNAs are important gene regulators with critical roles in diverse biological processes, including tumorigenesis. Several study's show that miR-139-5p is involved in the tumorigenesis and metastasis of various cancers. However, its expression and potential biologic role in endometrial cancer remain to be determined. This study aimed to investigate the miR-139-5p expression and to analyze its function and underlying molecular mechanism in endometrial cancer.
Methods:
Expression of miR-139-5p was measured using qRT-PCR. The expression of HOXA10 was detected by Immunofluorescence staining in endometrial cancer tissues and adjacent normal tissues. CCK-8 and colony formation assays were used to assess the effect of miR-139-5p on ECC1 and Ishikawa cell line proliferation. Transwell migration assay was used to study the effect of miR-139-5p on EC cell migration. Luciferase reporter assay and western blot were used to confirm targeting of HOXA10 by miR-139-5p.
Result:
We demonstrated that miR-139-5p was down-regulated in human endometrial cancer compared to their matched adjacent non-tumor tissues. Overexpressed miR-139-5p significantly inhibited endometrial cancer cell viability and migration. Computational algorithm in combination with dual luciferase reporter assays identified HOXA10 as the target of miR-139-5p. HOXA10 expression was downregulated in endometrial cancer cells after miR-139-5p overexpression. The expression level of HOXA10 was significantly increased in endometrial cancer tissues, which was inversely correlated with miR-139-5p expression in clinical endometrial cancer tissues.
Conclusion:
These findings indicate that miR-139-5p targets the HOXA10 transcript and suppresses endometrial cancer cell growth and migration, suggesting that miR-139-5p acts as a tumor suppressive role in human endometrial cancer pathogenesis.
Insights
MicroRNA miR-139-5p is downregulated in endometrial cancer, suppressing tumor growth and migration by targeting HOXA10. This finding highlights miR-139-5p as a potential therapeutic target for endometrial cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Endometrial cancer (EC) is a prevalent gynecological malignancy.
- MicroRNAs (miRNAs) are key regulators of gene expression implicated in cancer development.
- The role of miR-139-5p in endometrial cancer pathogenesis was previously undetermined.
Purpose of the Study:
- To investigate the expression levels of miR-139-5p in endometrial cancer.
- To elucidate the functional role and molecular mechanism of miR-139-5p in endometrial cancer.
- To identify potential downstream targets of miR-139-5p in endometrial cancer cells.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for miR-139-5p expression analysis.
- Immunofluorescence staining to detect HOXA10 expression in tumor tissues.
- Cell proliferation (CCK-8, colony formation) and migration (Transwell) assays to assess miR-139-5p function.
- Luciferase reporter and Western blot assays to validate HOXA10 as a direct target of miR-139-5p.
Main Results:
- miR-139-5p was significantly downregulated in human endometrial cancer tissues compared to adjacent normal tissues.
- Overexpression of miR-139-5p inhibited proliferation and migration of endometrial cancer cell lines (ECC1 and Ishikawa).
- HOXA10 was identified as a direct target of miR-139-5p, with its expression inversely correlated with miR-139-5p levels in clinical samples.
Conclusions:
- miR-139-5p functions as a tumor suppressor in endometrial cancer by targeting the HOXA10 transcript.
- Restoration of miR-139-5p expression may offer a therapeutic strategy for endometrial cancer.
- These findings provide novel insights into the molecular mechanisms underlying endometrial cancer progression.
More Related Videos
Related Concept Videos
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:40Cancer Stem Cells and Tumor Maintenance
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
01:02Role of Septins
Cellular Functions of Septins
Recent studies have revealed the multifaceted roles of septins in various cellular processes such as cytokinesis, ciliogenesis, and neurogenesis. Septins act as scaffolds and...
01:23The Role of Culture
01:21Role-Based Identity