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Long non-coding RNA Lnc-408 promotes invasion and metastasis of breast cancer cell by regulating LIMK1
- Source :
- Oncogene
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Invasion and metastasis are the leading causes of death in patients with breast cancer (BC), and epithelial-mesenchymal transformation (EMT) plays an essential role in this process. Here, we found that Lnc-408, a novel long noncoding RNA (lncRNA), is significantly upregulated in BC cells undergoing EMT and in BC tumor with lymphatic metastases compared with those without lymphatic metastases. Lnc-408 can enhance BC invasion and metastasis by regulating the expression of LIMK1. Mechanistically, Lnc-408 serves as a sponge for miR-654-5p to relieve the suppression of miR-654-5p on its target LIMK1. Knockdown or knockout of Lnc-408 in invasive BC cells clearly decreased LIMK1 levels, and ectopic Lnc-408 in MCF-7 cells increased LIMK1 expression to promote cell invasion. Lnc-408-mediated enhancement of LIMK1 plays a key role in cytoskeletal stability and promotes invadopodium formation in BC cells via p-cofilin/F-actin. In addition, the increased LIMK1 also facilitates the expression of MMP2, ITGB1, and COL1A1 by phosphorylating CREB. In conclusion, our findings reveal that Lnc-408 promotes BC invasion and metastasis via the Lnc-408/miR-654-5p/LIMK1 axis, highlighting a novel promising target for the diagnosis and treatment of BC.
- Subjects :
- Cancer Research
Epithelial-Mesenchymal Transition
MMP2
Apoptosis
Breast Neoplasms
LIMK1
CREB
Article
Non-coding RNAs
Metastasis
Breast cancer
Downregulation and upregulation
Cell Movement
Cell Line, Tumor
Genetics
medicine
Humans
Neoplasm Metastasis
Molecular Biology
Cell Proliferation
Gene knockdown
biology
Lim Kinases
medicine.disease
Long non-coding RNA
Up-Regulation
Gene Expression Regulation, Neoplastic
MicroRNAs
Lymphatic system
MCF-7 Cells
biology.protein
Cancer research
Female
RNA, Long Noncoding
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....93f63663be7f4c7ffb86b173cb03995a