ZFPM2-AS1 transcriptionally mediated by STAT1 regulates thyroid cancer cell growth, migration and invasion via miR-515-5p/TUSC3
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Updated: Nov 6, 2025

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Ruizhen Ren1, Yuanna Du2, Xing Niu3
1Department of Endocrinology, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai 264000, Shandong, China.
Abstract:
Objective: Our purpose was to study the roles and molecular mechanisms of long non-coding RNA (lncRNA) ZFPM2 Antisense RNA 1 (ZFPM2-AS1) in thyroid cancer. Methods: Firstly, the expression of ZFPM2-AS1, miR-515-5p and TUSC3 was detected in thyroid cancer tissues and cells. Secondary, their biological functions (proliferation, apoptosis, migration and invasion) were analyzed by a serious of functional experiments including cell counting kit-8 (CCK-8), clone formation, 5-Ethynyl-2'-deoxyuridine (EdU), enzyme-linked immunosorbent assay (ELISA), wound healing and Transwell assays. Thirdly, the mechanisms of STAT1/ZFPM2-AS1 and ZFPM2-AS1/miR-515-5p/TUSC were validated using chromatin immunoprecipitation (CHIP), pull-down and luciferase reporter assays. Results: ZFPM2-AS1 and TUSC were both highly expressed and miR-515-5p was down-regulated in thyroid cancer tissues as well as cells. Their knockdown weakened thyroid cancer cell growth, migration, and invasion. ZFPM2-AS1 was mainly distributed in the nucleus and cytoplasm of thyroid cancer cells. Mechanistically, up-regulation of ZFPM2-AS1 was induced by transcription factor STAT1 in line with CHIP and luciferase reporter assays. Furthermore, as a sponge of miR-515-5p, ZFPM2-AS1 decreased the ability of miR-515-5p to inhibit TUSC3 expression by pull-down, luciferase reporter and gain-and-loss assays, thereby promoting malignant progression of thyroid cancer. Conclusion: ZFPM2-AS1 acted as an oncogene in thyroid cancer, which was transcriptionally mediated by STAT1. Furthermore, ZFPM2-AS1 weakened the inhibitory effect of miR-515-5p on TUSC3. Thus, ZFPM2-AS1 could be an underlying biomarker for thyroid cancer.
Insights
Long non-coding RNA ZFPM2-AS1 promotes thyroid cancer by acting as an oncogene. It is regulated by STAT1 and sponges miR-515-5p, inhibiting TUSC3 expression and enhancing cancer progression.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Thyroid cancer is a significant health concern.
- Long non-coding RNAs (lncRNAs) play crucial roles in various cancers.
- The specific role of ZFPM2 Antisense RNA 1 (ZFPM2-AS1) in thyroid cancer requires further elucidation.
Purpose of the Study:
- To investigate the roles and molecular mechanisms of lncRNA ZFPM2-AS1 in thyroid cancer.
- To analyze the functional impact of ZFPM2-AS1 on thyroid cancer cell behavior.
- To elucidate the regulatory pathways involving ZFPM2-AS1, miR-515-5p, and TUSC3.
Main Methods:
- Expression analysis of ZFPM2-AS1, miR-515-5p, and TUSC3 in thyroid cancer tissues and cells.
- Functional assays including CCK-8, clone formation, EdU, ELISA, wound healing, and Transwell assays to assess cell proliferation, apoptosis, migration, and invasion.
- Mechanism validation using Chromatin Immunoprecipitation (CHIP), pull-down, and luciferase reporter assays.
Main Results:
- ZFPM2-AS1 and TUSC3 were upregulated, while miR-515-5p was downregulated in thyroid cancer.
- Knockdown of ZFPM2-AS1 inhibited thyroid cancer cell growth, migration, and invasion.
- ZFPM2-AS1, regulated by STAT1, acts as a sponge for miR-515-5p, reducing its inhibition on TUSC3 and promoting cancer progression.
Conclusions:
- ZFPM2-AS1 functions as an oncogene in thyroid cancer.
- STAT1 transcriptionally upregulates ZFPM2-AS1.
- ZFPM2-AS1 promotes thyroid cancer malignancy by sponging miR-515-5p and affecting TUSC3 expression, suggesting its potential as a biomarker.
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