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长链非编码RNA JPX通过靶向miR-33a-5p和PNMA1调控环调节骨肉瘤的恶性进展。

lncRNA JPX modulates malignant progress of osteosarcoma through targeting miR-33a-5p and PNMA1 regulatory loop.

作者信息

Xiong Wei, Liu Dan, Chen Xi, Liu Leiting, Xiao Weihong

机构信息

Department of General Vascular Surgery, Wuhan No.1 Hospital & Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, China.

Department of General Vascular Surgery, Wuhan No.1 Hospital & Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, China.

出版信息

Transl Oncol. 2022 Nov;25:101504. doi: 10.1016/j.tranon.2022.101504. Epub 2022 Sep 5.

Abstract

Osteosarcoma (OS) is a common type of bone tumor, present worldwide, that has distal metastasis ability. Although continuous development in cancer therapy has taken place, there are still no effective metastasis-curbing strategies for OS available. Hence, a better understanding of the biological characteristics and molecular mechanisms of OS carcinogenesis is urgently needed. Long noncoding RNAs (lncRNAs) have captured great interest among cancer scientists with considerable potential implications for cancer treatment. In this study, we found that lncRNA JPX was up-regulated in OS tissues and cells. We subsequently examined the functional role of JPX in OS cells through knocked-down JPX by using siRNA. JPX down-regulation was observed to suppress OS cell proliferation, migration and invasion. Furthermore, it was verified that JPX acts as a sponge for miR-33a-5p, and that JPX regulated OS cell proliferation, migration and invasion through miR-33a-5p. Moreover, down-regulation of miR-33a-5p in OS contributed to PNMA1 upregulation, and PNMA1 depletion inhibited OS cell proliferation, migration and invasion in vitro. Taken together, our data support an important role of JPX in regulating OS cell proliferation, invasion and migration that highlights JPX may be a potential therapeutic target for OS.

摘要

骨肉瘤(OS)是一种常见的骨肿瘤,在全球范围内均有发生,具有远端转移能力。尽管癌症治疗不断发展,但目前仍没有有效的骨肉瘤转移抑制策略。因此,迫切需要更好地了解骨肉瘤致癌的生物学特性和分子机制。长链非编码RNA(lncRNA)引起了癌症科学家的极大兴趣,对癌症治疗具有重要潜在意义。在本研究中,我们发现lncRNA JPX在骨肉瘤组织和细胞中上调。随后,我们通过使用小干扰RNA(siRNA)敲低JPX来研究其在骨肉瘤细胞中的功能作用。结果发现,JPX下调可抑制骨肉瘤细胞的增殖、迁移和侵袭。此外,证实JPX作为miR-33a-5p的海绵,通过miR-33a-5p调节骨肉瘤细胞的增殖、迁移和侵袭。此外,骨肉瘤中miR-33a-5p的下调导致PNMA1上调,而PNMA1的缺失在体外抑制了骨肉瘤细胞的增殖、迁移和侵袭。综上所述,我们的数据支持JPX在调节骨肉瘤细胞增殖、侵袭和迁移中起重要作用,这表明JPX可能是骨肉瘤的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bd5/9502696/ba6d45cba224/gr1.jpg

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