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Updated: May 23, 2025
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
POGZ targeted by LINC01355/miR-27b-3p retards thyroid cancer progression via interplaying with MAD2L2
Jiancan Lu1, Xinglu Zhou2, Hongling Zhu2
1Postgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical University, Shanghai, 200135 China.
Abstract:
Despite the high morbidity of thyroid cancer (THCA), the underlying molecular pathology remains elusive. That autism-associated protein POGZ has recently been involved in tumorigenesis intrigues us exploring its relevant molecular regulatory network in THCA. Clinical characteristics and intermolecular relationships were dissected by bioinformatics. Interaction between POGZ and MAD2L2 was examined by Co-IP assay. Targeting relationships between miR-27b-3p and POGZ/LINC01355 was verified by sequence prediction and dual-luciferase reporter detection. Cellular effects of genes were assessed by CCK-8 assay, clone formation assay, and Transwell assay, and further confirmed by a tumor-bearing nude mice model. Our results demonstrated a decrease in POGZ expression in THCA tissues and cell lines, and an interaction between POGZ and MAD2L2 protein. POGZ inhibited both the proliferation and motility of THCA cells, with these effects being reversed upon MAD2L2 silencing. LINC01355 exhibited low expression level and a positive correlation with POGZ in THCA. Both miR-27b-3p and LINC01355 were identified as regulators of POGZ through targeting. Elevated miR-27b-3p suppressed POGZ expression. LINC01355 promoted POGZ and counteracted the inhibitory effects of miR-27b-3p. Furthermore, miR-27b-3p increased the proliferation and motility of THCA cells, an effect that was blocked by LINC01355. At the animal level, POGZ, LINC01355, and MAD2L2 all attenuated tumor growth in THCA. Collectively, POGZ restrains THCA growth by interacting with MAD2L2 protein, and POGZ modulation involves a complex interplay orchestrated by LINC01355-targeted miR-27b-3p. By reporting the first POGZ-focused ceRNA network involving noncoding RNA in THCA, our study paves the way for exploring POGZ-related pathways and developing new therapeutic strategies in cancer.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s13205-025-04231-7.
Insights
The autism-associated protein POGZ restrains thyroid cancer (THCA) growth by interacting with MAD2L2. This complex regulatory network involves LINC01355 and miR-27b-3p, offering new therapeutic targets for THCA.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Thyroid cancer (THCA) poses a significant health burden, yet its molecular underpinnings remain incompletely understood.
- The autism-associated protein POGZ has emerged as a potential player in tumorigenesis, prompting investigation into its role in THCA.
- Understanding the regulatory network of POGZ in THCA is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To elucidate the molecular regulatory network of POGZ in thyroid cancer.
- To investigate the interaction between POGZ and MAD2L2 in THCA progression.
- To identify the roles of non-coding RNAs, specifically miR-27b-3p and LINC01355, in modulating POGZ expression and function in THCA.
Main Methods:
- Bioinformatic analysis of clinical characteristics and intermolecular relationships in THCA.
- Co-immunoprecipitation (Co-IP) assay to confirm POGZ-MAD2L2 protein interaction.
- Dual-luciferase reporter assays and sequence prediction to validate targeting relationships between miR-27b-3p, POGZ, and LINC01355.
- In vitro cellular assays (CCK-8, clone formation, Transwell) and in vivo tumor xenograft models in nude mice to assess gene functions.
Main Results:
- POGZ expression was significantly decreased in THCA tissues and cell lines.
- POGZ inhibited THCA cell proliferation and motility, with these effects reversed by MAD2L2 silencing.
- LINC01355 expression was low and positively correlated with POGZ in THCA.
- miR-27b-3p suppressed POGZ expression, while LINC01355 promoted POGZ and counteracted miR-27b-3p's inhibitory effects.
- Both POGZ and LINC01355 attenuated tumor growth in vivo, while elevated miR-27b-3p promoted THCA cell proliferation and motility.
Conclusions:
- POGZ acts as a tumor suppressor in THCA, inhibiting proliferation and motility through interaction with MAD2L2.
- A complex ceRNA network involving LINC01355, miR-27b-3p, and POGZ regulates THCA progression.
- This study reveals a novel POGZ-centered regulatory network in THCA, highlighting potential therapeutic targets for cancer treatment.
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