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微小RNA-128-3p通过靶向神经营养酪氨酸激酶受体3抑制恶性黑色素瘤细胞的恶性程度。

MiRNA-128-3p Restrains Malignant Melanoma Cell Malignancy by Targeting NTRK3.

作者信息

Zhou Xinxin, He Jiayuan, Wang Qingyuan, Ma Teng

机构信息

Academy of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, China.

Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, China.

出版信息

Front Oncol. 2021 Jan 26;10:538894. doi: 10.3389/fonc.2020.538894. eCollection 2020.

Abstract

The functions of non-coding RNA, including microRNA (miRNA), have attracted considerable attention in the field of oncology, In this report, we examined the roles and molecular mechanisms of miR-128-3p, as related to the biological behaviors of malignant melanoma (MM). We found that miR-128-3p was expressed in low levels in these MM cells and may serve as a tumor suppressor by inhibiting proliferation, migration, and invasion, as well as inducing apoptosis in these MM cells. Moreover, neurotrophin receptor 3 (NTRK3), which serves as an oncogene that can enhance malignant behaviors of MM cells, was up-regulated in MM cells. Our current survey disclosed a complementary binding between miR-128-3p and the NTRK3 3' untranslated regions (3'-UTR), while luciferase activities of NTRK3 3'-UTR were restrained by miR-128-3p in 293T cells. The effects of pre-miR-128-3p and sh-NTRK3 as well as anti-miR-128-3p and NTRK3(+) appeared to function synergistically in producing malignant progression. Moreover, there were possible to have counteracted effects for pre-miR-128-3p and NTRK3(+) in malignant progression. These findings established that miR-128-3p can function as a tumor suppressor by inhibiting carcinogenesis of the oncogene, NTRK3. Collectively, miR-128-3p and NTRK3 genes participate in modulating the malignant behavior of MM, and may represent new therapeutic targets for MM.

摘要

包括微小RNA(miRNA)在内的非编码RNA的功能在肿瘤学领域引起了相当大的关注。在本报告中,我们研究了miR-128-3p与恶性黑色素瘤(MM)生物学行为相关的作用和分子机制。我们发现miR-128-3p在这些MM细胞中低表达,并且可能通过抑制这些MM细胞的增殖、迁移和侵袭以及诱导凋亡来发挥肿瘤抑制作用。此外,神经营养因子受体3(NTRK3)作为一种可增强MM细胞恶性行为的癌基因,在MM细胞中上调。我们目前的研究揭示了miR-!28-3p与NTRK3 3'非翻译区(3'-UTR)之间的互补结合,而在293T细胞中,miR-128-3p抑制了NTRK3 3'-UTR的荧光素酶活性。前体miR-128-3p和短发夹RNA-NTRK3(sh-NTRK3)以及抗miR-128-3p和NTRK3(+)在产生恶性进展方面似乎具有协同作用。此外,前体miR-128-3p和NTRK3(+)在恶性进展中可能具有抵消作用。这些发现证实,miR-128-3p可通过抑制癌基因NTRK3的致癌作用发挥肿瘤抑制作用。总之,miR-128-3p和NTRK3基因参与调节MM的恶性行为,可能代表MM的新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6c/7871904/93451f0e272d/fonc-10-538894-g001.jpg

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