下调尿路上皮癌相关蛋白 1 可通过调控 miR-301a 和 CXCR4 抑制骨肉瘤 MHCC97 细胞的生长和迁移。

Knockdown of Urothelial Carcinoma-Associated 1 Suppressed Cell Growth and Migration Through Regulating miR-301a and CXCR4 in Osteosarcoma MHCC97 Cells.

机构信息

Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, P.R. China.

Department of General Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, P.R. China.

出版信息

Oncol Res. 2018 Dec 27;27(1):55-64. doi: 10.3727/096504018X15201143705855. Epub 2018 Mar 9.

Abstract

Liver cancer is one of the most common malignancies in the world and a leading cause of cancer-related mortality. Accumulating evidence has highlighted the critical role of long noncoding RNAs (lncRNAs) in various cancers. The present study aimed to explore the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in cell growth and migration in MHCC97 cells and its underlying mechanism. First, we assessed the expression of UCA1 in MHCC97 and three other cell lines by RT-qPCR. Then the expression of UCA1, miR-301a, and CXCR4 in MHCC97 cells was altered by transient transfection. The effects of UCA1 and miR-301 on cell viability, migration, invasion, and apoptosis were assessed. The results revealed that UCA1 expression was relatively higher in MHCC97 cells than in MG63, hFOB1.19, and OS-732 cells. Knockdown of UCA1 reduced cell viability, inhibited migration and invasion, and promoted cell apoptosis. However, the effect of UCA1 knockdown on cell growth and migration was blocked by miR-301a overexpression, whose expression was regulated by UCA1. We also found that miR-301a positively regulated CXCR4 expression. CXCR4 inhibition reversed the effect of miR-301a overexpression on cell growth and migration. Moreover, miR-301a activated the Wnt/β-catenin and NF-κB pathways via regulating CXCR4. The present study demonstrated that UCA1 inhibition exerted an antigrowth and antimigration role in MHCC97 cells through regulating miR-301a and CXCR4 expression.

摘要

肝癌是世界上最常见的恶性肿瘤之一,也是癌症相关死亡的主要原因。越来越多的证据表明长非编码 RNA(lncRNA)在各种癌症中起着关键作用。本研究旨在探讨 lncRNA 尿路上皮癌相关 1(UCA1)在 MHCC97 细胞中的细胞生长和迁移中的作用及其潜在机制。首先,我们通过 RT-qPCR 评估了 UCA1 在 MHCC97 和其他三种细胞系中的表达。然后,通过瞬时转染改变了 MHCC97 细胞中 UCA1、miR-301a 和 CXCR4 的表达。评估了 UCA1 和 miR-301 对细胞活力、迁移、侵袭和凋亡的影响。结果表明,UCA1 在 MHCC97 细胞中的表达相对高于 MG63、hFOB1.19 和 OS-732 细胞。敲低 UCA1 降低了细胞活力,抑制了迁移和侵袭,促进了细胞凋亡。然而,miR-301a 过表达阻断了 UCA1 敲低对细胞生长和迁移的影响,miR-301a 的表达受 UCA1 调节。我们还发现,miR-301a 正向调节 CXCR4 的表达。CXCR4 抑制逆转了 miR-301a 过表达对细胞生长和迁移的影响。此外,miR-301a 通过调节 CXCR4 激活了 Wnt/β-catenin 和 NF-κB 通路。本研究表明,UCA1 抑制通过调节 miR-301a 和 CXCR4 的表达对 MHCC97 细胞发挥抗生长和抗迁移作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0716/7848290/91b1bcfe54cc/OR-27-055-g001.jpg

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