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The LOXL1 antisense RNA 1 (LOXL1-AS1)/microRNA-423-5p (miR-423-5p)/ectodermal-neural cortex 1 (ENC1) axis promotes cervical cancer through the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway.
- Source :
-
Bioengineered [Bioengineered] 2022 Feb; Vol. 13 (2), pp. 2567-2584. - Publication Year :
- 2022
-
Abstract
- As the fourth commonest malignancy among females worldwide, cervical cancer (CC) poses a huge challenge to human health. The pivotal regulatory roles of lncRNAs in cancers have been highlighted. LOXL1 antisense RNA 1 (LOXL1-AS1) has been reported to play a key role in cervical squamous cell carcinoma and other various cancers. Thus, we investigated the roles and mechanisms of lncRNA LOXL1-AS1 in CC. The in vivo experiments demonstrated that LOXL1-AS1 downregulation inhibited tumor growth and metastasis and proliferation of CC cells. The results of RT-qPCR demonstrated that LOXL1-AS1 and ectodermal-neural cortex 1 (ENC1) expression levels were upregulated in CC cells and tissues, while microRNA-423-5p (miR-423-5p) level was downregulated. As subcellular fractionation assays, RNA pull down assays and luciferase reporter assays revealed, LOXL1-AS1 bound to miR-423-5p and miR-423-5p targeted ENC1. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, wound healing and colony formation assays demonstrated that miR-423-5p upregulation and LOXL1-AS1 downregulation inhibited CC cell proliferation and migration, while ENC1 upregulation attenuated the inhibitory effects of miR-423-5p upregulation on the malignant phenotypes of CC cells. Western blotting was conducted to measure protein levels and the results showed that ENC1 knockdown inhibited the activation of ERK/MEK pathway. In summary, the LOXL1-AS1/miR-423-5p/ENC1 axis accelerates CC development through the MEK/ERK pathway.
- Subjects :
- Female
HEK293 Cells
HeLa Cells
Humans
MicroRNAs genetics
Microfilament Proteins genetics
Neoplasm Proteins genetics
Neuropeptides genetics
Nuclear Proteins genetics
RNA, Antisense genetics
RNA, Neoplasm genetics
Uterine Cervical Neoplasms genetics
MAP Kinase Signaling System
MicroRNAs metabolism
Microfilament Proteins metabolism
Neoplasm Proteins metabolism
Neuropeptides metabolism
Nuclear Proteins metabolism
RNA, Antisense metabolism
RNA, Neoplasm metabolism
Uterine Cervical Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2165-5987
- Volume :
- 13
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Bioengineered
- Publication Type :
- Academic Journal
- Accession number :
- 35015607
- Full Text :
- https://doi.org/10.1080/21655979.2021.2018975