Long noncoding RNA APTR contributes to osteosarcoma progression through repression of miR‐132‐3p and upregulation of yes‐associated protein 1

• Published in: Journal of cellular physiology Vol. 234; no. 6; pp. 8998 - 9007
• Main Authors: Guan, Hongya, Shang, Guowei, Cui, Yuanbo, Liu, Jiu, Sun, Xiaoya, Cao, Wei, Wang, Yisheng, Li, Yuebai
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2019
• Subjects: 3' Untranslated Regions; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adolescent; Alu‐mediated p21 transcriptional regulator (APTR); Apoptosis; Binding Sites; Biocompatibility; Bone cancer; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Female; Gelatinase B; Gene Expression Regulation, Neoplastic; Humans; Ki-67 Antigen - genetics; Ki-67 Antigen - metabolism; Kinases; long noncoding RNAs (lncRNA); Male; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; miR‐132‐3p; Molecular modelling; Neoplasm Invasiveness; Osteosarcoma; osteosarcoma (OS); Osteosarcoma - genetics; Osteosarcoma - metabolism; Osteosarcoma - pathology; progression; Proteins; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Regulatory mechanisms (biology); Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Sarcoma; Signal Transduction; Transcription; Transcription Factors - genetics; Transcription Factors - metabolism; Up-regulation; Yap1 protein; Yes-associated protein; Yes‐associated protein 1 (YAP1); Yes-associated protein 1 (YAP1); progression; miR-132-3p; Alu-mediated p21 transcriptional regulator (APTR); osteosarcoma (OS); long noncoding RNAs (lncRNA)
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.27572

A growing amount of evidence has shown that long noncoding RNAs (lncRNAs) play crucial roles in osteosarcoma (OS). However, little knowledge is available about the functional roles and molecular mechanisms of lncRNA Alu‐mediated p21 transcriptional regulator (APTR) in OS. Herein, APTR expression was demonstrated to be significantly upregulated in OS tumor tissues and four OS cell lines (including MG63, 143B, Saos‐2, and HOS) compared with the adjacent tissues and human osteoblast cell line hFOB1.19, respectively. We confirmed miR‐132‐3p to be a target for APTR, and its expression was demonstrated to be inhibited by APTR. In functional terms, knockdown of APTR and overexpression of miR‐132‐3p both, remarkably repressed human OS cell proliferation, invasion and migration, and induced apoptosis. Also, Yes‐associated protein 1 (YAP1) was determined as an inhibitory target of miR‐132‐3p. Moreover, our findings demonstrated that the repression of YAP1 protein expression and the suppression of Ki‐67, MMP9, and Bcl2 expression induced by APTR knockdown required increased miR‐132‐3p. Thus, APTR contributed to OS progression through repression of miR‐132‐3p and upregulation of YAP1 expression. Therefore, we have uncovered a novel regulatory mechanism by which the APTR/miR‐132‐3p/YAP1 axis can regulate OS progression. In summary, our study was the first to establish that Alu‐mediated p21 transcriptional regulator (APTR) can function as an oncogenic long noncoding RNA in osteosarcoma (OS). Most importantly, we explored a new regulatory mechanism of the APTR/miR‐132‐3p/Yes‐associated protein 1 axis in the regulation of OS cells, which could be a potential therapeutic biomarker for OS.