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FOXP1-induced lncRNA CLRN1-AS1 acts as a tumor suppressor in pituitary prolactinoma by repressing the autophagy via inactivating Wnt/β-catenin signaling pathway.
- Source :
-
Cell death & disease [Cell Death Dis] 2019 Jun 24; Vol. 10 (7), pp. 499. Date of Electronic Publication: 2019 Jun 24. - Publication Year :
- 2019
-
Abstract
- As the commonest type of functional pituitary tumor, prolactinoma takes up around 40-60% of functional pituitary tumors. Despite dedications attributed to the treatment of prolactinoma, complete cure remains difficult. Hence, it is of significance to bring to light the underlying mechanism of prolactinoma. Long noncoding RNAs (lncRNAs) are a group of transcripts which can regulate various biological processes. In the present study, we explored an lncRNA that was differentially downregulated in prolactinoma samples. LncRNA clarin 1 antisense RNA 1 (CLRN1-AS1) was downregulated in 42 patient samples and inactivated the Wnt/β-catenin signaling pathway. Functionally, CLRN1-AS1 suppressed cell proliferation, promoted apoptosis, and inhibited autophagy. Subcellular fractionation assay revealed that CLRN1-AS1 was located in the cytoplasm of prolactinoma cells. Based on bioinformatics analysis and mechanism experiments, we determined that CLRN1-AS1 acted as a competing endogenous RNA (ceRNA) by sponging miR-217 to upregulate the dickkopf WNT signaling pathway inhibitor 1 (DKK1). Furthermore, Forkhead box P1 (FOXP1) was verified to be a transcription suppressor of CLRN1-AS1. In summary, this study revealed that FOXP1-induced CLRN1-AS1 regulated cellular functions in pituitary prolactinoma by sponging miR-217 to release the DKK1/Wnt/β-catenin signaling pathway.
- Subjects :
- Animals
Autophagy genetics
Autophagy physiology
Blotting, Western
Caspase 3 metabolism
Chromatin Immunoprecipitation
Computational Biology
Forkhead Transcription Factors genetics
Gene Expression Regulation, Neoplastic genetics
Gene Expression Regulation, Neoplastic physiology
Humans
Immunoprecipitation
In Situ Hybridization, Fluorescence
In Vitro Techniques
Male
Mice
Mice, Inbred BALB C
Pituitary Neoplasms genetics
Prolactinoma genetics
RNA, Long Noncoding genetics
Real-Time Polymerase Chain Reaction
Repressor Proteins genetics
Wnt Signaling Pathway genetics
Wnt Signaling Pathway physiology
beta Catenin genetics
Forkhead Transcription Factors metabolism
Membrane Proteins genetics
Pituitary Neoplasms metabolism
Pituitary Neoplasms pathology
Prolactinoma metabolism
Prolactinoma pathology
RNA, Long Noncoding metabolism
Repressor Proteins metabolism
beta Catenin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 10
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 31235696
- Full Text :
- https://doi.org/10.1038/s41419-019-1694-y