Linc00423 as a tumor suppressor in retroperitoneal liposarcoma via activing MAPK signaling pathway through destabilizing of NFATC3

• Published in: Cell death & disease 2019-06, Vol.10 (6), p.430-430, Article 430
• Main Authors: Zhang, Yong, Tong, Hanxing, He, Junyi, Shao, Yebo, Guo, Xi, Zhuang, Rongyuan, Yang, Jue, Liu, Ju, Ding, Yuqin, Liu, Wenshuai, Lu, Weiqi, Zhou, Yuhong
• Format: Article
• Language: English
• Subjects: 13; 14; 38; 631/67/1798; 631/67/69; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell Proliferation - genetics; Computer applications; Female; Gastric cancer; Gene expression; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; HEK293 Cells; Humans; Immunology; Life Sciences; Liposarcoma; Liposarcoma - genetics; Liposarcoma - metabolism; MAP kinase; MAP Kinase Signaling System - genetics; Mice; Mice, Inbred BALB C; Mice, Nude; Next-generation sequencing; NFATC Transcription Factors - genetics; NFATC Transcription Factors - metabolism; Nucleotide sequence; Post-transcription; Protein Binding; Retroperitoneal Neoplasms - genetics; Retroperitoneal Neoplasms - metabolism; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA-Seq; Signal transduction; Transplantation, Heterologous; Tumor suppressor genes; Up-Regulation - genetics
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-019-1658-2

Unraveling the noncoding RNA expression networks governing cancer initiation and development is essential while remains largely uncompleted in retroperitoneal liposarcoma (RLS). Through RNA-seq technologies and computational biology, deregulated long noncoding RNAs (lncRNAs) are being identified and reveal that lncRNAs are implicated in serial steps of RLS development. High-throughput sequencing with computational methods for assembling the transcriptome of five paired RLS patient’s tissues. We found that long intergenic noncoding RNA 423 (linc00423) was downregulated in RLS tissues. Gain-of-function assays revealed that overexpressed linc00423 obviously inhibited RLS cell growth in vitro and in vivo. Additionally, RNA sequence, RNA-pulldown and RIP assays evidenced that linc00423 involved in MAPK signaling pathway via destabilizing of nuclear factor of activated T-cells 3 (NFATC3). Summing up, our findings demonstrated that linc00423 acted as the tumor suppressor in RLS cells through regulating the protein level of NFATC3 at a post-transcriptional level and negatively regulated the MAPK signaling pathway at a transcriptional level. Linc00423 might serve as a candidate prognostic biomarker and a target for novel therapies of RLS patients.