lncRNA XIST通过调控miR-1269b/SOX6抑制乳腺癌生长、迁移和侵袭的研究

Long non-coding RNA XIST inhibited breast cancer cell growth,migration,and invasion via miR-1269b/SOX6 axis

目的探讨上链非编码RNA(long non-coding RNA,lnc RNA)XIST在乳腺癌病程中的生物学功能及作用机制。方法通过qRT-PCR检测乳癌组织及癌旁组织中lncRNA XIST(以下简称XIST)的表达;CCK-8检测低表达XIST后乳腺癌细胞的活性变化,AO/EB检测乳腺癌细胞凋亡情况。Wound healing和Trans well检测XIST在卵巢癌细胞中侵袭以及迁移的能力。生物信息学方法以及Luciferace确定XIST的潜在靶向作用。结果在乳腺癌组织和相关的乳腺癌细胞系中,XIST表达明显下调(P<0.05);进一步功能性分析实验显示,过表达XIST可以明显抑制乳腺癌的生长、迁移和侵袭。Luciferace实验结果证实miR-1269b为XIST的下游作用靶点。此外,SOX6是miR-1269b的下游作用靶点;并且在乳腺癌细胞系中调控miR-1269b/SOX6可以逆转XIST的功能。结论XIST在乳腺癌患者中明显下调,上调XIST可以通过调控miR-1269b和SOX6的表达来抑制乳腺癌的生长、迁移和侵袭。

Objective To explore the biological function and mechanism of lncRNA XIST in breast cancer.Method QRT-PCR was used to detect the expression of lncRNA XIST in breast cancer tissues.The cell viability was tested by CCK-8 after up-regulate XIST.The apoptosis of breast cancer cells was detected by AO/EB.Wound healing and trans well were used to detect the invasion and migration of XIST in ovarian cancer cells.Bioinformatics and Luciferace assay was used to determine the potential targeting effect of XIST.Results XIST was significantly down-regulated in breast cancer tissues and cell lines(P<0.05).Further functional analysis indicated that overexpression of XIST remarkably inhibited breast cancer cell growth,migration,and invasion.The results of luciferase reporter assays verified that miR-1269b was a direct target of XIST in breast cancer.Moreover,SOX6 was identified as a direct target of miR-1269b and miR-1269b/SOX6 rescued the effects of XIST in breast cancer cells.Conclusion XIST is down-regulated in breast cancer and suppresses breast cancer cell growth,migration,and invasion via the miR-1269b/SOX6 axis.