Abstract
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.
Graphical abstract
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.
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The datasets generated/analyzed during the current study are available.
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Change history
14 August 2023
A Correction to this paper has been published: https://doi.org/10.1007/s10565-023-09824-7
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This study was supported by the project of the Shenzhen Science and Technology Commission (JCYJ20190809112803651).
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Shaoying Li, Jiamei Hu, and Guisen Li wrote the paper. Huifen Mai, Yinfei Gao, and Bichan Liang conceived the experiments. Huacong Wu and Jianling Guo analyzed the data. Yuan Duan, Shaoying Li, and and Jiamei Hu collected and provided the sample for this study. All authors have read and approved the final submitted manuscript.
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Fig. S1 LAMA2 mRNA and protein expressions in breast cancer samples with different molecular types by RT-qPCR and Western blot. Note: A, RT-qPCR was used to detect the mRNA expression of LAMA2 in breast cancer samples with different molecular types; B: Western blot was used to detect the protein expression of LAMA2 in breast cancer samples with different molecular types; each sample was repeated three times (PNG 299 kb)
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Li, S., Hu, J., Li, G. et al. Epigenetic regulation of LINC01270 in breast cancer progression by mediating LAMA2 promoter methylation and MAPK signaling pathway. Cell Biol Toxicol 39, 1359–1375 (2023). https://doi.org/10.1007/s10565-022-09763-9
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DOI: https://doi.org/10.1007/s10565-022-09763-9