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hsa_circ_0136666 的上调通过海绵吸附 miR-1299 和靶向 CDK6 促进乳腺癌进展。

Upregulation of hsa_circ_0136666 contributes to breast cancer progression by sponging miR-1299 and targeting CDK6.

机构信息

Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.

出版信息

J Cell Biochem. 2019 Aug;120(8):12684-12693. doi: 10.1002/jcb.28536. Epub 2019 Apr 16.

DOI:10.1002/jcb.28536
PMID:30993801
Abstract

Circular RNAs (circRNAs) can participate in multiple cancers, including breast cancer. Increasing circRNAs are recognized in various cancers because of the high-throughput sequencing. However, the potential physiological effect of hsa_circ_0136666 in breast cancer progression is unknown. In our study, the biological role of hsa_circ_0136666 in breast cancer development was studied. It was displayed that hsa_circ_0136666 was greatly increased in breast cancer. In addition, overexpression of hsa_circ_0136666 was able to promote Michigan Cancer Foundation-7 (MCF7) and BT474 cell proliferation and triggered cell cycle in G2/M phase. microRNA plays critical role in tumor development and they can act as direct targets of circRNAs. miR-1299 has been implicated as a famous tumor suppressor in many cancers. Here, miR-1299 was predicted as the target of hsa_circ_0136666. Meanwhile, its Upregulation repressed breast cancer proliferation, migration and invasion capacity, which could be reversed by the increase of hsa_circ_0136666. Furthermore, Cyclin-dependent kinase 6 (CDK6) was speculated as the downstream target of miR-1299. In MCF7 and BT474 cells, CDK6 was greatly overexpressed and it was shown that CDK6 contributed a lot to breast cancer progression. Subsequently, it was implied that hsa_circ_0136666 could modulate CDK6 levels positively in vitro. In conclusion, it was revealed that Upregulation of hsa_circ_0136666 promoted breast cancer progression by sponging miR-1299 and targeting CDK6.

摘要

环状 RNA(circRNAs)可以参与多种癌症,包括乳腺癌。由于高通量测序,越来越多的 circRNAs 在各种癌症中被发现。然而,hsa_circ_0136666 在乳腺癌进展中的潜在生理效应尚不清楚。在本研究中,研究了 hsa_circ_0136666 在乳腺癌发展中的生物学作用。结果显示,hsa_circ_0136666 在乳腺癌中大量增加。此外,hsa_circ_0136666 的过表达能够促进 Michigan Cancer Foundation-7(MCF7)和 BT474 细胞的增殖,并触发 G2/M 期细胞周期。microRNA 在肿瘤发展中起着关键作用,它们可以作为 circRNAs 的直接靶标。miR-1299 已被认为是许多癌症中的一种著名的肿瘤抑制因子。在这里,miR-1299 被预测为 hsa_circ_0136666 的靶标。同时,其上调抑制了乳腺癌的增殖、迁移和侵袭能力,而 hsa_circ_0136666 的增加可以逆转这种能力。此外,推测细胞周期蛋白依赖性激酶 6(CDK6)是 miR-1299 的下游靶标。在 MCF7 和 BT474 细胞中,CDK6 大量过表达,表明 CDK6 对乳腺癌的发展有很大贡献。随后,暗示 hsa_circ_0136666 可以在体外正向调节 CDK6 水平。总之,研究结果表明,hsa_circ_0136666 通过海绵吸附 miR-1299 和靶向 CDK6 来促进乳腺癌的进展。

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