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

IF 2.3 3区 医学 Q3 ONCOLOGY
Xi Lin, Zhi Yan, Ling Hai, Yan Niu, Jian-Xun Wen, Hong-Zhe Zhu, Cheng Yan, Su-Na Cha, Li Yan, Wen-Qi Zheng, Man Zhang, Zhi-De Hu
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引用次数: 0

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.

miR-146a靶向的Sortilin-1调控非小细胞肺癌的行为
背景:SORT1参与多种恶性肿瘤的发病机制,但其在非小细胞肺癌(NSCLC)中的作用尚不清楚。方法:采用免疫组化方法比较SORT1在癌组织和癌旁非癌组织中的表达。用miR-146a模拟物或SORT1小干扰RNA (siRNA)处理NSCLC细胞系,包括A549、H1299和PC-9,然后使用细胞计数试剂盒-8、transwell试验和抓伤试验评估细胞活性、迁移、侵袭和凋亡。此外,采用生物信息学方法预测miR-146a靶基因,随后通过双荧光素酶报告基因检测进行验证。结果:与邻近的非癌组织相比,SORT1在NSCLC组织中显著升高。下调SORT1可抑制肿瘤细胞系的增殖、侵袭、迁移,促进细胞凋亡。此外,SORT1是miR-146a的直接靶点。MiR-146a通过抑制SORT1的表达调节肿瘤细胞的增殖、迁移、侵袭和凋亡。结论:这些结果表明miR-146a通过靶向SORT1在NSCLC的发病机制中起着关键作用,突出了其作为NSCLC治疗靶点的潜力。
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来源期刊
Thoracic Cancer
Thoracic Cancer ONCOLOGY-RESPIRATORY SYSTEM
CiteScore
5.20
自引率
3.40%
发文量
439
审稿时长
2 months
期刊介绍: Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed. The editors encourage contributions relevant to prevention, general thoracic surgery, medical oncology, radiology, radiation medicine, pathology, basic cancer research, as well as epidemiological and translational studies in thoracic cancer. Thoracic Cancer is the official publication of the Chinese Society of Lung Cancer, International Chinese Society of Thoracic Surgery and is endorsed by the Korean Association for the Study of Lung Cancer and the Hong Kong Cancer Therapy Society. The Journal publishes a range of article types including: Editorials, Invited Reviews, Mini Reviews, Original Articles, Clinical Guidelines, Technological Notes, Imaging in thoracic cancer, Meeting Reports, Case Reports, Letters to the Editor, Commentaries, and Brief Reports.
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