FOXP1-induced LncRNA CLRN1-AS1 Acts As a Tumor Suppressor in Pituitary Prolactinoma by Repressing the Autophagy Via Inactivating Wnt/β-catenin Signaling Pathway

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2019 Jun 26

PMID 31235696

Citations 35

Authors

Chao Wang

Chunlei Tan

Yuan Wen

Dongzhi Zhang

Guofu Li

Liang Chang

Jun Su

Xin Wang

Affiliations

Soon will be listed here.

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.

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