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Published on: August 2, 2024
MiR-3666 serves as a tumor suppressor in ovarian carcinoma by down-regulating AK4 via targeting STAT3
Huiping Tan1, Chunlin Wu2, Bo Huang1
1Reproductive Medicine Center, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Abstract:
As a result of metastasis and high recurrence, ovarian carcinoma (OC) is one of the most frequent gynecological carcinomas affecting women up to now. In spite of advances in OC treatments, the molecular mechanisms underlying OC progression are still needed to be deeply understood. MicroRNAs (miRNAs) with aberrant expressions are widely known to regulate target genes so as to mediate diverse biological activities of tumor cells. In the present study, we inspected the expression profile and latent mechanism of miR-3666 in OC. First of all, our research revealed the down-regulated miR-3666 in OC cells. Furthermore, miR-3666 up-regulation could repress cell proliferation and migration as well as induce cell apoptosis in OC. In addition, we unmasked that miR-3666 targeted STAT3 (signal transducer and activator of transcription 3) and further down-regulated STAT3 expression. Moreover, adenylate kinase 4 (AK4) was transcriptionally enhanced by STAT3, and then miR-3666 restrained AK4 expression by mediating STAT3. In the end, rescue experiments depicted that miR-3666 suppressed the development of OC via STAT3-mediated AK4. We uncovered that miR-3666 inhibited the tumorigenesis and even development of OC via suppressing STAT3/AK4 axis, offering a novel biomarker and therapeutic target for OC.
Insights
MicroRNA-3666 (miR-3666) is down-regulated in ovarian carcinoma (OC). Restoring miR-3666 suppresses OC development by targeting the STAT3/AK4 pathway, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ovarian carcinoma (OC) is a frequent gynecological cancer with high recurrence rates.
- Understanding the molecular mechanisms of OC progression is crucial for developing effective treatments.
- MicroRNAs (miRNAs) play significant roles in regulating tumor cell activities.
Purpose of the Study:
- To investigate the expression profile and underlying mechanism of miR-3666 in ovarian carcinoma.
- To determine the role of miR-3666 in OC cell proliferation, migration, and apoptosis.
- To elucidate the molecular targets and pathways regulated by miR-3666 in OC.
Main Methods:
- Analysis of miR-3666 expression in OC cells.
- Assessment of miR-3666's effects on OC cell proliferation, migration, and apoptosis.
- Identification of miR-3666 targets using molecular assays.
- Investigation of the STAT3 and AK4 interaction with miR-3666.
- Rescue experiments to validate the miR-3666/STAT3/AK4 axis in OC development.
Main Results:
- miR-3666 expression was found to be down-regulated in OC cells.
- Up-regulation of miR-3666 inhibited OC cell proliferation and migration, and induced apoptosis.
- miR-3666 directly targets STAT3 (signal transducer and activator of transcription 3), down-regulating its expression.
- STAT3 enhances adenylate kinase 4 (AK4) transcription; miR-3666 restrains AK4 expression by modulating STAT3.
- Rescue experiments confirmed that miR-3666 suppresses OC development via the STAT3-mediated AK4 pathway.
Conclusions:
- miR-3666 acts as a tumor suppressor in ovarian carcinoma.
- The miR-3666/STAT3/AK4 axis is a key pathway involved in OC tumorigenesis.
- miR-3666 represents a potential novel biomarker and therapeutic target for ovarian carcinoma.
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