Expression signature of lncRNA APTR in clinicopathology of breast cancer: Its potential oncogenic function in dysregulation of ErbB signaling pathway

Abstract

A growing amount of evidence has revealed that long noncoding RNAs (lncRNAs) play significant roles in malignancies through different mechanisms especially the competing endogenous RNA (ceRNA). They have also been shown to have the potential diagnostic, prognostic and therapeutic biomarker capacity in oncology research. Recently, lncRNA Alu-mediated p21 transcriptional regulator (APTR) has been proposed as an oncogenic lncRNA in development and clinical outcome of some cancers. However, clinical and molecular importance in breast cancer (BC) is still unclear. The purpose of this study was to examine the APTR expression and its potential roles in BC. The 47 BC tumors and 47 tumor adjacent normal tissues were obtained from the study subjects. Real-time PCR was applied for the analysis of APTR expression in breast tumors compared with paired adjacent normal tissues. Then, we used bioinformatics approach to investigate the potential ceRNA activity of APTR in APTR-microRNAs-mRNAs axes and with focus on ErbB signaling pathway in BC. Our results demonstrated that APTR expression was significantly upregulated in BC tumors compared with the adjacent normal tissues. Besides, APTR over-expression was related to a larger tumors size. Finally, bioinformatics analysis indicated that APTR could influence cell proliferation through dysregulating the oncogenes working in ErbB signaling pathway by sponging some tumor suppressive microRNAs (miRNAs). Current work provided some clues for the involvement of APTR in physiopathology of the breast tumors. However, other aspects of these findings need to be further elucidated by future functional studies.

Identification and Roles of miR-29b-1-3p and miR29a-3p-Regulated and Non-Regulated lncRNAs in Endocrine-Sensitive and Resistant Breast Cancer Cells

“…Bioinformatic analysis identified ten miRNAs as putative APRT interactors, but miR-29 was not included [ 76 ]. APTR was demonstrated to repress CDKN1A transcription by binding to the promoter and recruiting the PRC2 complex [ 77 ].…”

“…APTR was demonstrated to repress CDKN1A transcription by binding to the promoter and recruiting the PRC2 complex [ 77 ]. APTR was recently reported to be increased in breast tumors compared to normal adjacent breast tissue and to be higher in larger tumors, suggesting an oncogenic function [ 76 ]. Another recent study reported that APTR directly interacts with ERα in Ht-UtLM human leiomyoma cells [ 78 ].…”

Low expression of lncRNA APTR promotes gastric cancer progression

“…LncRNA Alu-mediated p21 transcriptional regulator (APTR), which suppresses the CDKN1A/p21 promoter, was found to regulate cell proliferation in several cancers, such as human glioma [9] , osteosarcoma [10] , breast cancer [11] , thyroid cancer [12] and hepatic stellate cells [13] . In this study, we investigated lncRNA APTR's role in GC, which was lower expressed in gastric tumor tissues than in gastric normal tissues.…”

Circular RNA‐associated ceRNA network involved in HIF‐1 signalling in triple‐negative breast cancer: circ_0047303 as a potential key regulator

“…These non‐coding RNAs interact with each other and orchestrate significant processes such as metastasis in cancer cells. 14 , 15 One of the functions of circRNAs is to sponge miRNAs, which in turn affects the expression of their target mRNAs. 16 Such interactions have been investigated in the context of competing endogenous RNA (ceRNA) regulatory networks in BC.…”