An antisense RNA capable of modulating the expression of the tumor suppressor microRNA-34a

• Published in: Cell death & disease 2018-07, Vol.9 (7), p.736-15, Article 736
• Main Authors: Serviss, Jason T., Andrews, Nathanael, Van den Eynden, Jimmy, Richter, Felix Clemens, Houtman, Miranda, Vesterlund, Mattias, Schwarzmueller, Laura, Johnsson, Per, Larsson, Erik, Grandér †, Dan, Pokrovskaja Tamm, Katja
• Format: Article
• Language: English
• Subjects: 13/44; 38/77; 38/89; 42/109; 45/90; Antibodies; Antisense RNA; Biochemistry; Biomedical and Life Sciences; Cancer; Cancer and Oncology; Cancer och onkologi; Cell Biology; Cell Culture; cell lung-cancer; Cellular stress response; differentiation; gene; hepatocellular-carcinoma; human genome; Immunology; Life Sciences; long noncoding rnas; Medicin och hälsovetenskap; MicroRNAs; mir-34a; miRNA; ms-gf plus; neuronal; p53 Protein; protein; Solid tumors; transcriptional activation; Tumor suppressor genes; Tumorigenesis
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-0777-5

The microRNA-34a is a well-studied tumor suppressor microRNA (miRNA) and a direct downstream target of TP53 with roles in several pathways associated with oncogenesis, such as proliferation, cellular growth, and differentiation. Due to its broad tumor suppressive activity, it is not surprising that miR34a expression is altered in a wide variety of solid tumors and hematological malignancies. However, the mechanisms by which miR34a is regulated in these cancers is largely unknown. In this study, we find that a long noncoding RNA transcribed antisense to the miR34a host gene, is critical for miR34a expression and mediation of its cellular functions in multiple types of human cancer. We name this long noncoding RNA lncTAM34a , and characterize its ability to facilitate miR34a expression under different types of cellular stress in both TP53 -deficient and wild-type settings.