SLC34A2通过激活STX17介导的食管鳞状细胞癌自噬促进细胞增殖

IF 2.3 3区 医学 Q3 ONCOLOGY
Thoracic Cancer Pub Date : 2024-06-01 Epub Date: 2024-05-08 DOI:10.1111/1759-7714.15314
Yi Xu, Shiyu Duan, Wen Ye, Zhousan Zheng, Jiaxing Zhang, Ying Gao, Sheng Ye
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引用次数: 0

摘要

背景:溶质运载家族 34 成员 2 (SLC34A2) 与多种恶性肿瘤的发病有关。然而,SLC34A2在食管鳞状细胞癌(ESCC)中的临床意义和潜在分子机制仍不明确:方法:采用Western印迹、定量实时PCR和免疫组织化学方法评估SLC34A2 mRNA/蛋白在ESCC细胞系或组织中的表达水平。采用 Kaplan-Meier 曲线进行生存分析。为确定 SLC34A2 对 ESCC 细胞增殖的影响,进行了 CCK-8、集落形成、EdU 和异种移植肿瘤模型试验。使用流式细胞仪检测细胞周期。进行了 RNA 序列分析和富集分析,以探索潜在的信号通路。通过Western印迹、mRFP-GFP-LC3报告系统和透射电子显微镜评估了自噬通量。免疫沉淀法和质谱法用于鉴定潜在的 SLC34A2 相互作用蛋白。通过环己亚胺(CHX)追逐和泛素化实验检测蛋白质的稳定性:结果:SLC34A2在ESCC中的表达明显上调,并与ESCC患者的不良临床病理特征,尤其是Ki-67标记指数和不良预后相关。过表达 SLC34A2 会促进 ESCC 细胞增殖,而沉默 SLC34A2 则会产生相反的效果。此外,SLC34A2诱导自噬促进ESCC细胞增殖,而抑制自噬则抑制ESCC细胞增殖。进一步的研究表明,SLC34A2与自噬相关蛋白STX17相互作用,通过抑制STX17的泛素化和降解,促进ESCC细胞的自噬和增殖:这些研究结果表明,SLC34A2 可作为 ESCC 的预后生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SLC34A2 promotes cell proliferation by activating STX17-mediated autophagy in esophageal squamous cell carcinoma.

Background: Solute carrier family 34 member 2 (SLC34A2) has been implicated in the development of various malignancies. However, the clinical significance and underlying molecular mechanisms of SLC34A2 in esophageal squamous cell carcinoma (ESCC) remain elusive.

Methods: Western blotting, quantitative real-time PCR and immunohistochemistry were utilized to evaluate the expression levels of SLC34A2 mRNA/protein in ESCC cell lines or tissues. Kaplan-Meier curves were employed for survival analysis. CCK-8, colony formation, EdU and xenograft tumor model assays were conducted to determine the impact of SLC34A2 on ESCC cell proliferation. Cell cycle was examined using flow cytometry. RNA-sequencing and enrichment analysis were carried out to explore the potential signaling pathways. The autophagic flux was evaluated by western blotting, mRFP-GFP-LC3 reporter system and transmission electron microscopy. Immunoprecipitation and mass spectrometry were utilized for identification of potential SLC34A2-interacting proteins. Cycloheximide (CHX) chase and ubiquitination assays were conducted to test the protein stability.

Results: The expression of SLC34A2 was significantly upregulated in ESCC and correlated with unfavorable clinicopathologic characteristics particularly the Ki-67 labeling index and poor prognosis of ESCC patients. Overexpression of SLC34A2 promoted ESCC cell proliferation, while silencing SLC34A2 had the opposite effect. Moreover, SLC34A2 induced autophagy to promote ESCC cell proliferation, whereas inhibition of autophagy suppressed the proliferation of ESCC cells. Further studies showed that SLC34A2 interacted with an autophagy-related protein STX17 to promote autophagy and proliferation of ESCC cells by inhibiting the ubiquitination and degradation of STX17.

Conclusions: These findings indicate that SLC34A2 may serve as a prognostic biomarker for ESCC.

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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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