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微小RNA-486通过调节蛋白激酶C-δ途径抑制骨肉瘤的发展。

miR-486 suppresses the development of osteosarcoma by regulating PKC-δ pathway.

作者信息

He Ming, Wang Guangbin, Jiang Linlin, Qiu Chuang, Li Bin, Wang Jiashi, Fu Yonghui

机构信息

Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, P.R. China.

Department of Electrotheropy, Shenyang Medical College Affiliated Central Hospital, Shenyang, Liaoning, P.R. China.

出版信息

Int J Oncol. 2017 May;50(5):1590-1600. doi: 10.3892/ijo.2017.3928. Epub 2017 Mar 22.

Abstract

Osteosarcoma is one of the most highly malignant types of cancer in adolescents and young adults with a high mortality rate. Despite advances in surgery, radiation therapy and chemotherapy, the prognosis for patients with osteosarcoma has not significantly improved over the past several decades. It is necessary to find new indicators of prognosis and therapeutic targets of osteosarcoma. Through the analysis of 40 osteosarcoma tissues, we found that the expression of miR‑486 was low and the expression of PKC‑δ was high in osteosarcoma. Median survival of patients with low expression of miR-486 (30 months) was shorter than the patients with higher expression of miR‑486 (40 months). We further found that miR-486 can inhibit the targeting of PKC‑δ signaling pathways, and this inhibition can inhibit the growth and invasion of osteosarcoma cells. After transfection of miR‑486 for 24 h, the proliferation of osteosarcoma cells was inhibited by ~20%, and the migration was inhibited by ~15%. In the present investigation, we demonstrated that miR‑486 is negatively associated with the expression of PKC-δ and could regulate the development of osteosarcoma. miR-486 may be a potential target for the treatment of osteosarcoma.

摘要

骨肉瘤是青少年和年轻成年人中恶性程度最高的癌症类型之一,死亡率很高。尽管在手术、放射治疗和化疗方面取得了进展,但在过去几十年中,骨肉瘤患者的预后并未得到显著改善。有必要寻找骨肉瘤新的预后指标和治疗靶点。通过对40例骨肉瘤组织的分析,我们发现骨肉瘤中miR-486表达较低,PKC-δ表达较高。miR-486低表达患者的中位生存期(30个月)短于miR-486高表达患者(40个月)。我们进一步发现,miR-486可以抑制PKC-δ信号通路的靶向作用,这种抑制作用可以抑制骨肉瘤细胞的生长和侵袭。转染miR-486 24小时后,骨肉瘤细胞的增殖受到约20%的抑制,迁移受到约15%的抑制。在本研究中,我们证明miR-486与PKC-δ的表达呈负相关,并可调节骨肉瘤的发展。miR-486可能是治疗骨肉瘤的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/977c/5403184/b9444ae292d5/IJO-50-05-1590-g00.jpg

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