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.
Highlights
Pituitary adenoma, the second commonest cancer in the central nervous system which takes up 14% in intracranial neoplasm, has an overall prevalence around 1/1500 persons[1,2]
We applied microarray analysis to find out Long noncoding RNAs (lncRNAs) that were differentially expressed in pituitary prolactinoma samples
Site 5 was responsible for the transcription inhibition of Forkhead box part 1 (P1) (FOXP1) on CLRN1-AS1. All these findings suggested that FOXP1-induced CLRN1-AS1 suppressed cell growth in pituitary prolactinoma by acting as a competing endogenous RNA (ceRNA) to regulate the dickkopf WNT signaling pathway inhibitor 1 (DKK1)/Wnt/β-catenin signaling pathway (Fig. 8)
Summary
The second commonest cancer in the central nervous system which takes up 14% in intracranial neoplasm, has an overall prevalence around 1/1500 persons[1,2]. Pituitary prolactinoma is the most prevalent type, occupying about 40–60% of all functional pituitary tumors[3]. Exploring the molecular mechanism involved in the initiation or progression of pituitary prolactinoma is of great. Dysregulation of lncRNAs in malignancies can promote or suppress tumorigenesis[8,9,10,11]. Some researchers reported that lncRNAs can exert tumor suppressive or oncogenic roles in pituitary prolactinoma[12,13,14]. The mechanism and function of lncRNAs in pituitary prolactinoma remain largely unknown. The aim of this study is to explore the function and molecular mechanism of a novel
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