乳腺癌的LINC01270表观调控通过介导LAMA2启动子甲基化和MAPK信号通路。
Epigenetic regulation of LINC01270 in breast cancer progression by mediating LAMA2 promoter methylation and MAPK signaling pathway.
发表日期:2022 Oct 14
作者:
Shaoying Li, Jiamei Hu, Guisen Li, Huifen Mai, Yinfei Gao, Bichan Liang, Huacong Wu, Jianling Guo, Yuan Duan
来源:
CELL BIOLOGY AND TOXICOLOGY
摘要:
长链非编码RNA(lncRNA)在乳腺癌(BC)调节中的应用受到了很多关注。在这里,我们探讨了长间隔非编码RNA 01270(LINC01270)在BC中的作用和潜在机制。通过生物信息学工具的帮助,我们识别出属于牛皮蛋白亚单位α2(LAMA2)的乳腺癌相关差异表达基因,以便辨别LAMA2在BC细胞中的作用。BC细胞最初表达不充分,而LINC01270高度表达。随后,对BC细胞进行了sh-LINC01270或/和sh-LAMA2处理,以探索它们在BC中的调节机制。这揭示了LINC01270抑制上调了LAMA2并且使MAPK信号通路失活来抑制BC细胞的恶性特征。功能测定表明,LINC01270结合到DNMT1、DNMT3a和DNMT3b促进了LAMA2启动子中CpG岛的甲基化并抑制LAMA2表达。此外,我们的数据表明,LAMA2通过抑制MAPK信号通路抑制BC细胞的恶性特征。体外结果在体内实验的帮助下得到了重复。总之,LINC01270沉默抑制了LAMA2启动子的甲基化,以抑制MAPK信号通路的活化,从而抑制了BC进展。1、过表达LAMA2抑制BC细胞的恶性特征。2、LINC01270通过招募DNMTs到LAMA2启动子区域促进LAMA2启动子甲基化。3、5-aza-dc逆转了LINC01270促进LAMA2启动子甲基化的作用。4、LAMA2通过抑制MAPK信号通路抑制BC细胞的恶性特征。 © 2022年。作者(s)已独家授权给Springer Nature B.V。
Application of long non-coding RNAs (lncRNAs) for modulation of breast cancer (BC) has attracted much attention. Here, we probed into the role and underlying mechanism of long intergenic non-coding RNA 01270 (LINC01270) in BC. With the help of bioinformatics tools, we identified laminin subunit alpha 2 (LAMA2) as a BC-related differentially expressed gene to discern the effect of LAMA2 in BC cells. LAMA2 was initially poorly expressed while LINC01270 was highly expressed in BC. BC cells were subsequently treated with sh-LINC01270 or/and sh-LAMA2 for exploration of their regulatory mechanism in BC, which unfolded that LINC01270 inhibition up-regulated LAMA2 and inactivated the MAPK signaling pathway to suppress malignant characteristics of BC cells. Functional assays demonstrated that LINC01270 bound to DNMT1, DNMT3a, and DNMT3b promoted the methylation of CpG islands in LAMA2 promoter and inhibited the LAMA2 expression. Moreover, our data suggested that LAMA2 suppressed MAPK signaling pathway to inhibit BC cell malignant characteristics. The in vitro results were re-produced with the help of the in vivo experimentations. In conclusion, LINC01270 silencing inhibited the methylation of LAMA2 promoter to suppress the activation of MAPK signaling pathway, which subsequently restrained the BC progression. 1, Overexpression of LAMA2 inhibits malignant features of BC cells. 2, LINC01270 promotes LAMA2 promoter methylation by recruiting DNMTs to the LAMA2 promoter region. 3, 5-aza-dc reverses the promotion of LAMA2 promoter methylation by LINC01270. 4, LAMA2 inhibits malignant features of BC cells by suppressing the activation of MAPK signaling pathway.© 2022. The Author(s), under exclusive licence to Springer Nature B.V.