miR-20a-5p inhibits endometrial cancer progression by targeting janus kinase 1
1Department of Gynaecology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, P.R. China.
Abstract:
Endometrial cancer (EC) is a multi-factorial disease of which pathogenesis has not been fully elucidated. The function and underlying mechanism of microRNA-20a-5p (miR-20a-5p) in EC remain poorly understood. The present study aimed to analyze the association between miR-20a-5p expression and the clinicopathological characteristics of patients with EC. Whether miR-20a-5p could inhibit EC progression by targeting janus kinase 1 (Jak1) was subsequently investigated. To do so, human EC tissues and paracancerous tissues were collected from 47 patients with EC. miR-20a-5p and Jak1 mRNA and protein expression was determined by reverse transcription quantitative PCR and western blotting, respectively. Cell proliferation, invasive ability and adhesion were investigated by MTT, Matrigel invasion and cell adhesion assays, respectively. Dual luciferase reporter assay was used to verify whether miR-20a-5p could directly target Jak1. The results demonstrated that miR-20a-5p was downregulated and that Jak1 was upregulated in EC tissues compared with paracancerous tissues. In addition, miR-20a-5p expression and Jak1 expression level were negatively correlated in EC tissues. miR-20a-5p expression was also significantly associated with the depth of myometrial invasion, FIGO stage, histologic grade and lymph node metastasis in patients with EC. Furthermore, Jak1 was identified as a new direct target of miR-20a-5p, and Jak1 overexpression was demonstrated to reverse the effects of miR-20a-5p-mimic on EC cell proliferation, invasive ability and adhesion. Taken together, the results from this study revealed for the first time that miR-20a-5p expression was significantly associated with the clinicopathological characteristics of patients with EC. These findings suggested that miR-20a-5p may act as a tumor suppressor in EC, in part through decreasing Jak1 expression. miR-20a-5p and Jak1 may therefore serve as potential therapeutic targets in EC.
Insights
MicroRNA-20a-5p (miR-20a-5p) is downregulated in endometrial cancer (EC), acting as a tumor suppressor by inhibiting janus kinase 1 (Jak1). This finding suggests miR-20a-5p and Jak1 as potential EC therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Endometrial cancer (EC) pathogenesis is complex and not fully understood.
- The role of microRNA-20a-5p (miR-20a-5p) in EC progression remains unclear.
- Investigating microRNAs offers potential for novel diagnostic and therapeutic strategies in cancer.
Purpose of the Study:
- To analyze the association between miR-20a-5p expression and clinicopathological characteristics in EC patients.
- To determine if miR-20a-5p inhibits EC progression by targeting janus kinase 1 (Jak1).
- To elucidate the functional mechanism of miR-20a-5p in endometrial cancer.
Main Methods:
- Reverse transcription quantitative PCR and western blotting to assess miR-20a-5p and Jak1 expression in EC tissues.
- Cellular assays (MTT, Matrigel invasion, adhesion) to evaluate the impact of miR-20a-5p on EC cell behavior.
- Dual luciferase reporter assay to confirm direct targeting of Jak1 by miR-20a-5p.
Main Results:
- miR-20a-5p was significantly downregulated, while Jak1 was upregulated in EC tissues compared to adjacent normal tissues.
- A negative correlation was observed between miR-20a-5p and Jak1 expression in EC tissues.
- miR-20a-5p expression correlated significantly with myometrial invasion depth, FIGO stage, histologic grade, and lymph node metastasis.
- Jak1 was validated as a direct target of miR-20a-5p, and its overexpression reversed miR-20a-5p-mimic effects on EC cell proliferation and invasion.
Conclusions:
- miR-20a-5p functions as a tumor suppressor in endometrial cancer, partly by downregulating Jak1 expression.
- miR-20a-5p expression is significantly associated with key clinicopathological features of EC.
- Both miR-20a-5p and Jak1 represent promising therapeutic targets for endometrial cancer treatment.
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