Sortilin-1, Targeted by miR-146a, Regulates the Behavior of Non-Small Cell Lung Cancer

Sep 23, 2026

Background: Sortilin-1 (SORT1) is implicated in diverse malignancies, yet its function in non-small cell lung cancer (NSCLC) needs clarification. Methods: Immunohistochemistry quantified SORT1 in tumor versus adjacent tissues. NSCLC cell lines were treated with miR-146a mimics or SORT1 siRNA, then assessed for viability, migration, invasion, and apoptosis; bioinformatics predicted miR-146a targets, verified by dual-luciferase assays. Results: SORT1 was elevated in NSCLC; its downregulation suppressed proliferation, migration, invasion, and promoted apoptosis. Conclusion: miR-146a promotes NSCLC pathogenesis by targeting SORT1, supporting therapeutic potential.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

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Introduction

Lung cancer overview and need for new targets

Sortilin-1 (SORT1) and miRNA regulation background

MicroRNAs (miRNAs) and target prediction rationale

Thoracic Cancer ORIGINAL ARTICLE OPEN ACCESS Sortilin-1, Targeted by miR-146a, Regulates the Behavior of Non-Small Cell Lung Cancer Xi Lin1 | Zhi Yan2,3,4 | Ling Hai5,6 | Yan Niu3,7 | Jian-Xun Wen3,7 | Hong-Zhe Zhu2,3 | Cheng Yan2,3 | Su-Na Cha2,3 | Li Yan3,8 | Wen-Qi Zheng2,3 | Man Zhang1,9 | Zhi-De Hu2,3,10 1Department of Thoracic Surgery, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China | 2Department of Laboratory Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China | 3Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, China | 4School of Medical Laboratory, Tianjin Medical University, Tianjin, China | 5Department of Pathology, Basic Medical College, Inner Mongolia Medical University, Hohhot, China | 6Department of Pathology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China | 7Public Service Center for Medical Research, Inner Mongolia Medical University, Hohhot, China | 8Department of Respiratory and Critical Care Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China | 9Department of Thoracic Surgery and Oncology, the Key Laboratory of Advanced Interdisciplinary Studies, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China | 10Center for Clinical Epidemiology Research, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China Correspondence: Man Zhang ([284248563@qq.com](284248563@qq.com)) | Zhi-De Hu ([hzdlj81@163.com](hzdlj81@163.com)) Received: 25 April 2025 | Revised: 26 June 2025 | Accepted: 1 July 2025 Funding: This work was supported by the Natural Science Foundation of Inner Mongolia Autonomous Region of China (2024MS08055) . Keywords: miR-146a | NSCLC | sortilin-1 ABSTRACT Background: Sortilin-1 (SORT1) has been implicated in the pathogenesis of various malignancies, but its role in non-small cell lung cancer (NSCLC) remains to be elucidated. Methods: Immunohistochemistry was employed to assess the expression of SORT1 in cancerous tissues compared to adjacent non-cancerous tissues. NSCLC cell lines, including A549, H1299, and PC-9, underwent treatment with miR-146a mimics or SORT1 small interfering RNA (siRNA), followed by evaluations of cell viability, migration, invasion, and apoptosis using cell counting kit-8, transwell assays, and scratch wound assays. Additionally, bioinformatic methods were employed to predict miR- 146a target genes, which were subsequently validated through dual-luciferase reporter assays. Results: SORT1 was significantly elevated in NSCLC tissues compared to adjacent non-cancerous counterparts. Downregulation of SORT1 inhibited proliferation, invasion, migration of tumor cell lines and promoted apoptosis. Moreover, SORT1 was a direct target of miR-146a. MiR-146a modulated tumor cell proliferation, migration, invasion, and apoptosis by suppressing SORT1 expression. Conclusion: These results suggest that miR-146a plays a critical role in the pathogenesis of NSCLC by targeting SORT1, highlighting its potential as a therapeutic target for NSCLC. | Xi Lin and Zhi Yan contributed equally to this work. | | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2025 The Author(s) . Thoracic Cancer published by John Wiley & Sons Australia, Ltd. | Thoracic Cancer, 2025; 16:e70129 1 of 11 [https://doi.org/10.1111/1759-7714.70129](https://doi.org/10.1111/1759-7714.70129) 1 | Introduction Lung cancer is among the most prevalent malignancies globally and constitutes a principal cause of cancer-related mortality [1, 2] . Approximately 85% of

FAQs

What is the main biological question of the study?

How Sortilin-1 (SORT1) is regulated by miR-146a and how this axis affects the behavior of non-small cell lung cancer (NSCLC).

How did the researchers measure SORT1 expression and function?

They used immunohistochemistry to compare SORT1 in NSCLC tissues versus adjacent non-cancerous tissues, and performed functional assays after miR-146a mimic or SORT1 siRNA treatment.

What conclusions link miR-146a to NSCLC progression?

The study found miR-146a directly targets SORT1 and that modulating SORT1 expression changes NSCLC cell proliferation, migration, invasion, and apoptosis, supporting miR-146a/SORT1 as a therapeutic target.

Sep 23, 2026

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