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抑制微小RNA-15b-5p通过调节/STAT3轴减弱口腔鳞状细胞癌的进展。

Inhibition of microRNA-15b-5p Attenuates the Progression of Oral Squamous Cell Carcinoma via Modulating the /STAT3 Axis.

作者信息

Liu Xuerong, Dong Yuanyuan, Song Dan

机构信息

Department of Oral and Maxillofacial Surgery, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277100, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Oct 28;12:10559-10572. doi: 10.2147/CMAR.S272498. eCollection 2020.

Abstract

BACKGROUND

Emerging evidence has demonstrated the important functions of microRNAs (miRNAs) in human malignancies. This study focuses on the function of miR-15b-5p on the oral squamous cell carcinoma (OSCC) progression and the molecules involved.

METHODS

Tumor and the paracancerous tissues were obtained from OSCC patients. Differentially expressed miRNAs between the tumor and normal tissues were screened out. miR-15b-5p expression in tumors and acquired cells was determined, and its correlation with patient survival was analyzed. Knockdown of miR-15b-5p was introduced in SCC-4 and CAL-27 cells to explore its role in cell growth and metastasis. Binding relationship between miR-15b-5p and was validated, and altered expression of was introduced in cells to explore its function in OSCC development. Xenograft tumors were induced in nude mice for in vivo experiments.

RESULTS

miR-15b-5p was abundantly expressed in OSCC tumors and cells and linked to poor survival in patients. Silencing of miR-15b-5p suppressed proliferation, migration, and invasion and triggered apoptosis in SCC-4 and CAL-27 cells. miR-15b-5p targeted . Further silencing of blocked the inhibiting functions of miR-15b-5p inhibitor in OSCC cell growth. The in vitro results were reproduced in vivo, where inhibition of miR-15b-5p led to a decline in tumor growth and metastasis in nude mice. was found as a negative mediator of the STAT3 pathway.

CONCLUSION

This study evidenced that miR-15b-5p possibly promotes OSCC development through binding to and the following STAT3 signaling activation. miR-15b-5p may be a potential therapeutic target for OSCC.

摘要

背景

新出现的证据表明微小RNA(miRNA)在人类恶性肿瘤中具有重要功能。本研究聚焦于miR-15b-5p在口腔鳞状细胞癌(OSCC)进展中的作用及相关分子。

方法

从OSCC患者获取肿瘤组织和癌旁组织。筛选出肿瘤组织与正常组织中差异表达的miRNA。测定肿瘤组织及获得性细胞中miR-15b-5p的表达,并分析其与患者生存的相关性。在SCC-4和CAL-27细胞中敲低miR-15b-5p,以探究其在细胞生长和转移中的作用。验证miR-15b-5p与[此处原文缺失相关分子名称]的结合关系,并在细胞中导入[此处原文缺失相关分子名称]的表达变化,以探究其在OSCC发生发展中的功能。在裸鼠中诱导异种移植瘤进行体内实验。

结果

miR-15b-5p在OSCC肿瘤组织和细胞中高表达,且与患者不良生存相关。沉默miR-15b-5p可抑制SCC-4和CAL-27细胞的增殖、迁移和侵袭,并引发细胞凋亡。miR-15b-5p靶向[此处原文缺失相关分子名称]。进一步沉默[此处原文缺失相关分子名称]可阻断miR-15b-5p抑制剂对OSCC细胞生长的抑制作用。体外实验结果在体内得到重现,抑制miR-15b-5p可导致裸鼠肿瘤生长和转移减少。[此处原文缺失相关分子名称]被发现是STAT3信号通路的负向调节因子。

结论

本研究证明miR-15b-5p可能通过与[此处原文缺失相关分子名称]结合并随后激活STAT3信号通路促进OSCC的发展。miR-15b-5p可能是OSCC潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844f/7604544/6f210e05f9fe/CMAR-12-10559-g0001.jpg

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