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环状 RNA SLC8A1 通过海绵吸附 miR-671 调控 PTEN/PI3k/Akt 通路抑制乳腺癌发生发展

circSLC8A1 sponges miR-671 to regulate breast cancer tumorigenesis via PTEN/PI3k/Akt pathway.

机构信息

Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, PR China.

Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, 410008, Hunan Province, PR China.

出版信息

Genomics. 2021 Jan;113(1 Pt 1):398-410. doi: 10.1016/j.ygeno.2020.12.006. Epub 2020 Dec 8.

Abstract

Breast cancer is the most frequently diagnosed and the leading cause of cancer-related deaths in women worldwide. However, the role of circSLC8A1 in breast cancer remains elusive. Herein, a cohort of 77 breast tumors and paired adjacent normal mammary tissues were collected. We demonstrated that circSLC8A1 was significantly down-regulated in breast cancer tissues and cell lines, of which expression was negatively correlated with clinical severity and dismal prognosis. Overexpression of circSLC8A1 suppressed cell proliferation, migration and invasion in vitro, and inhibited tumor growth in vivo. CircSLC8A1 directly targeted miR-671 to execute tumor suppressive activities via regulating PI3k/Akt signaling. Krüppel-like factor 16 (KLF16), a transcriptional activator of PTEN, was identified as a target of miR-671. Furthermore, circSLC8A1 could sponge miR-671 to suppress breast tumor growth via PTEN/PI3k/Akt signaling in vivo. In summary, circSLC8A1/miR-671 regulates breast cancer progression through PTEN/PI3k/Akt signaling, which may provide efficient therapeutic target for this devastating cancer.

摘要

乳腺癌是全球女性最常见的癌症诊断和癌症相关死亡的主要原因。然而,circSLC8A1 在乳腺癌中的作用仍不清楚。本研究收集了 77 例乳腺癌肿瘤和配对的相邻正常乳腺组织。我们证明 circSLC8A1 在乳腺癌组织和细胞系中显著下调,其表达与临床严重程度和预后不良呈负相关。circSLC8A1 的过表达抑制了体外细胞增殖、迁移和侵袭,并抑制了体内肿瘤生长。circSLC8A1 可以通过调节 PI3k/Akt 信号通路直接靶向 miR-671 来发挥肿瘤抑制活性。Krüppel 样因子 16(KLF16)是 PTEN 的转录激活因子,被鉴定为 miR-671 的靶基因。此外,circSLC8A1 可以通过体内的 PTEN/PI3k/Akt 信号通路来抑制 miR-671 从而抑制乳腺癌肿瘤的生长。总之,circSLC8A1/miR-671 通过 PTEN/PI3k/Akt 信号通路调节乳腺癌的进展,这可能为这种毁灭性的癌症提供有效的治疗靶点。

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