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LINC00313通过靶向miR-320b和MITF促进胆管癌的侵袭性和肿瘤发生。

LINC00313 promotes the aggressiveness and tumorigenesis of cholangiocarcinoma through targeting miR-320b and MITF.

作者信息

Wang Ziyu, Li Jiao, Xu Jing, Wan Tingqiu, Ya Yunjin, Li Xi, Wang Xi, Jin Yan

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming, 650100, Yunnan, China.

出版信息

Discov Oncol. 2025 May 7;16(1):680. doi: 10.1007/s12672-025-02472-9.

DOI:10.1007/s12672-025-02472-9
PMID:40332479
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12058610/
Abstract

OBJECTIVE

Cholangiocarcinoma, a cancer of the biliary duct, is frequently diagnosed in advanced stages with poor prognosis. Understanding the molecular mechanisms driving its progression is crucial for developing effective treatment approaches. This research delves into the role of LINC00313 in regulating the aggressiveness of cholangiocarcinoma cells.

METHODS

Clinical samples were collected to examine the expression pattern of LINC00313, miR-320b, and MITF using RT-qPCR and western blot analysis. Functional experiments, including cell proliferation, migration, and invasion assays, as well as apoptosis detection, were performed to assess the malignant properties of cholangiocarcinoma cells. The tumorigenic potential of cholangiocarcinoma cells was further investigated in a xenograft mouse model.

RESULTS

Elevated levels of LINC00313 were detected in both cholangiocarcinoma tumors and cell lines. Knocking down LINC00313 reduced the aggressiveness of cholangiocarcinoma cells and hindered their ability to form tumors in vivo. It was discovered that miR-320b is a target of LINC00313, exhibiting an expression pattern and functional role that contrasts with LINC00313. Moreover, the LINC00313/miR-320b axis was found to regulate the expression of MITF, thereby influencing the aggressiveness of cholangiocarcinoma cells.

CONCLUSION

LINC00313/miR-320b/MITF axis is implicated in the malignant progression of cholangiocarcinoma, indicating the potential of targeting LINC00313 as a strategy for cholangiocarcinoma clinical management.

摘要

目的

胆管癌是一种胆管癌症,通常在晚期被诊断出来,预后较差。了解驱动其进展的分子机制对于开发有效的治疗方法至关重要。本研究深入探讨了LINC00313在调节胆管癌细胞侵袭性中的作用。

方法

收集临床样本,采用逆转录定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹分析来检测LINC00313、miR-320b和小眼相关转录因子(MITF)的表达模式。进行了包括细胞增殖、迁移和侵袭试验以及细胞凋亡检测在内的功能实验,以评估胆管癌细胞的恶性特性。在异种移植小鼠模型中进一步研究胆管癌细胞的致瘤潜力。

结果

在胆管癌肿瘤和细胞系中均检测到LINC00313水平升高。敲低LINC00313可降低胆管癌细胞的侵袭性,并阻碍其在体内形成肿瘤的能力。发现miR-320b是LINC00313的一个靶点,其表达模式和功能作用与LINC00313相反。此外,发现LINC00313/miR-320b轴调节MITF的表达,从而影响胆管癌细胞的侵袭性。

结论

LINC00313/miR-320b/MITF轴与胆管癌的恶性进展有关,表明靶向LINC00313作为胆管癌临床治疗策略的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/7a28093a3e4d/12672_2025_2472_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/7463cdbd3232/12672_2025_2472_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/d1bb69c4177d/12672_2025_2472_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/fe1b5d0a9ee5/12672_2025_2472_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/0685e2c6f50f/12672_2025_2472_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/eb45d846d759/12672_2025_2472_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/7a28093a3e4d/12672_2025_2472_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/7463cdbd3232/12672_2025_2472_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/c8c5f43f78a5/12672_2025_2472_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/0ae90ecf0216/12672_2025_2472_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/d1bb69c4177d/12672_2025_2472_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/fe1b5d0a9ee5/12672_2025_2472_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/0685e2c6f50f/12672_2025_2472_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/eb45d846d759/12672_2025_2472_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5710/12058610/7a28093a3e4d/12672_2025_2472_Fig8_HTML.jpg

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本文引用的文献

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EMBO Rep. 2024 Mar;25(3):1022-1054. doi: 10.1038/s44319-024-00075-z. Epub 2024 Feb 8.
2
LINC00313 promotes the proliferation and inhibits the apoptosis of chondrocytes via regulating miR-525-5p/GDF5 axis.LINC00313 通过调控 miR-525-5p/GDF5 轴促进软骨细胞增殖并抑制其凋亡。
J Orthop Surg Res. 2023 Feb 24;18(1):137. doi: 10.1186/s13018-023-03610-1.
3
Survival and Causes of Death among Patients with Intrahepatic Cholangiocarcinoma in the United States from 2000 to 2018.
2000 年至 2018 年美国肝内胆管癌患者的生存和死亡原因。
Cancer Epidemiol Biomarkers Prev. 2022 Dec 5;31(12):2169-2176. doi: 10.1158/1055-9965.EPI-22-0444.
4
Chemotherapeutic resistant cholangiocarcinoma displayed distinct intratumoral microbial composition and metabolic profiles.化疗耐药性胆管癌表现出明显的肿瘤内微生物组成和代谢特征。
PeerJ. 2022 Aug 16;10:e13876. doi: 10.7717/peerj.13876. eCollection 2022.
5
Cancer cell-derived exosomal LINC00313 induces M2 macrophage differentiation in non-small cell lung cancer.肿瘤细胞衍生的外泌体 LINC00313 诱导非小细胞肺癌中 M2 型巨噬细胞分化。
Clin Transl Oncol. 2022 Dec;24(12):2395-2408. doi: 10.1007/s12094-022-02907-7. Epub 2022 Aug 18.
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LINC00313 facilitates osteosarcoma carcinogenesis and metastasis through enhancing EZH2 mRNA stability and EZH2-mediated silence of PTEN expression.LINC00313 通过增强 EZH2 mRNA 的稳定性和 EZH2 介导的沉默 PTEN 表达促进骨肉瘤的发生和转移。
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