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LINC01278在骨肉瘤中高表达，并通过介导miR-134-5p/KRAS轴参与肿瘤的发生发展。

LINC01278 is Highly Expressed in Osteosarcoma and Participates in the Development of Tumors by Mediating the miR-134-5p/KRAS Axis.

作者信息

Zhang Guo-Feng, Zhou Bai-Sui, An Xiao-Chun, An Feng-Min, Li Shan-Hui

机构信息

Department of Orthopedics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 261400, People's Republic of China.

出版信息

Onco Targets Ther. 2021 Jan 26;14:683-695. doi: 10.2147/OTT.S265591. eCollection 2021.

DOI:10.2147/OTT.S265591
PMID:33531816
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7847385/
Abstract

PURPOSE

There is increasing evidence that non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), produce a critical regulatory effect on osteosarcoma (OS). LINC01278, as a newly discovered lncRNA, is found to be highly expressed in OS, but its related mechanism remains unclear. This research, therefore, is designed to study the mechanism of LINC01278 in OS and to find potential targets for clinical use.

METHODS

qRT-PCR was applied to determine the relative expression of LINC01278 and analyze its diagnostic value in OS. CCK-8, Transwell and flow cytometry were utilized for the determination of cell proliferation, migration/invasion, and apoptosis. RIP and RNA pull-down experiments were used to verify the targeted binding effect of miR-134-5p and LINC01278. The relationship between miR-134-5p and LINC01278 or KRAS was analyzed using dual luciferase reporter gene. The effects of LINC01278 on tumor growth in nude mice was analyzed by in vivo experiment.

RESULTS

qRT-PCR showed that LINC01278 increased in OS tissues and serum, indicating poor prognosis. In addition, LINC01278 was also of high value for OS diagnosis. Functional experiments showed that LINC01278 inhibited KRAS-mediated OS cell proliferation and metastasis through miR-134-5p. Finally, the results of an in vivo animal model indicated that LINC01278 promoted OS growth.

CONCLUSION

LINC01278 is expressed highly in OS, and patients with high LINC01278 expression have poor prognosis. Moreover, LINC01278 can suppress the proliferation and apoptosis of OS cells through mediating miR-134-5p/KRAS axis, which is expected to become a potential therapeutic target for OS.

摘要

目的

越来越多的证据表明，包括长链非编码RNA（lncRNAs）和微小RNA（miRNAs）在内的非编码RNA（ncRNAs）对骨肉瘤（OS）产生关键的调节作用。LINC01278作为一种新发现的lncRNA，在OS中高表达，但其相关机制尚不清楚。因此，本研究旨在探讨LINC01278在OS中的作用机制，并寻找潜在的临床应用靶点。

方法

应用qRT-PCR检测LINC01278的相对表达，并分析其在OS中的诊断价值。采用CCK-8、Transwell和流式细胞术检测细胞增殖、迁移/侵袭和凋亡情况。通过RIP和RNA下拉实验验证miR-134-5p与LINC01278的靶向结合作用。利用双荧光素酶报告基因分析miR-134-5p与LINC01278或KRAS之间的关系。通过体内实验分析LINC01278对裸鼠肿瘤生长的影响。

结果

qRT-PCR显示，LINC01278在OS组织和血清中表达增加，提示预后不良。此外，LINC01278对OS诊断也具有较高价值。功能实验表明，LINC01278通过miR-134-5p抑制KRAS介导的OS细胞增殖和转移。最后，体内动物模型结果表明，LINC01278促进OS生长。

结论

LINC01278在OS中高表达，LINC01278高表达患者预后不良。此外，LINC01278可通过介导miR-134-5p/KRAS轴抑制OS细胞的增殖和凋亡，有望成为OS的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5193/7847385/9a0cbabe68c7/OTT-14-683-g0008.jpg
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