Targeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular

Xue Yang1,2,3, Yonglin Wu1,2,3, Shaojie Xu1,2,3

  • 1Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

Abstract

Insights

Thyroid cancer redifferentiation strategies may target Kir5.1 (KCNJ16), a gene downregulated in tumors. This study identifies Kir5.1 as a potential therapeutic target for recurrent and metastatic thyroid cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Recurrent and metastatic thyroid cancer presents aggressive characteristics, including dedifferentiation, significantly reducing survival rates.
  • The thyroid-stimulating hormone receptor (TSHR) is crucial for thyroid cell differentiation.
  • Identifying novel therapeutic targets is essential for improving outcomes in advanced thyroid cancer.

Purpose of the Study:

  • To identify potential therapeutic targets for thyroid cancer redifferentiation strategies.
  • To investigate the role of TSHR in thyroid cancer differentiation.
  • To explore novel therapeutic avenues for recurrent and metastatic thyroid cancer.

Main Methods:

  • Integrated gene expression data from public databases (GEO, TCGA) to identify differentially expressed genes related to TSHR.
  • Performed functional enrichment analysis and validated gene expression using RT-PCR in patient tissues.
  • Utilized AI-enabled virtual screening and molecular docking (VirtualFlow) to identify potential drug candidates targeting identified genes.

Main Results:

  • Identified five key genes (KCNJ16, SLC26A4, TG, TPO, SYT1) as potential therapeutic targets.
  • Found significant downregulation of TSHR and KCNJ16 in thyroid tumor tissues compared to normal tissues.
  • KCNJ16 (encoding Kir5.1) showed reduced expression in invasive tumors and is implicated in cell growth and differentiation; AI docking identified potent Kir5.1 inhibitors.

Conclusions:

  • Kir5.1 (KCNJ16) is a promising therapeutic target for redifferentiation strategies in recurrent and metastatic thyroid cancer.
  • This research provides insights into TSHR's role in thyroid cancer differentiation.
  • The identified Kir5.1 targeting molecules warrant further investigation for clinical application.

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