1. Lncrnas as potential targets in small cell lung cancer: Myc-dependent regulation
- Author
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Kubilay Inci, Pervin Elvan Tokgun, Onur Tokgun, and Hakan Akca
- Subjects
Cancer Research ,Lung Neoplasms ,Overexpression ,cyclin D1 ,Apoptosis ,MYC ,UCA1 gene ,E2F4AS gene ,SNHG6 gene ,Western blotting ,Small hairpin RNA ,0302 clinical medicine ,cell growth assay ,HOTAIR gene ,transcription factor Sox2 ,Tumor Cells, Cultured ,PVT1 gene ,Inhibition ,MEG3 ,0303 health sciences ,MALAT1 ,Molecular Structure ,Cell Cycle ,Neat1 gene ,apoptosis ,SCLC ,HOTAIR ,Cell cycle ,cell invasion ,PVT1 ,unclassified drug ,ANRIL gene ,oncogene myc ,real time polymerase chain reaction ,030220 oncology & carcinogenesis ,Molecular Medicine ,RNA, Long Noncoding ,cell cycle ,Lentiviral vector ,lentivirus vector ,down regulation ,H19 gene ,protein bcl 2 ,gene overexpression ,long untranslated RNA ,Sox2OT gene ,Antineoplastic Agents ,Biology ,SNHG3 gene ,Article ,Malat1 gene ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,Structure-Activity Relationship ,L1PA16 gene ,nerve cell adhesion molecule ,Cancer stem cell ,GAS5 gene ,Humans ,BC200 gene ,controlled study ,human ,gene ,AK23948 gene ,030304 developmental biology ,Cell Proliferation ,Pharmacology ,Dose-Response Relationship, Drug ,SFMBT2 gene ,human cell ,MEG3 gene ,PTENP1 gene ,ZEB2NAT gene ,Small Cell Lung Carcinoma ,LncRNA ,cell proliferation ,Myc protein ,Cancer research ,gene expression ,small cell lung cancer ,GAS5 ,Drug Screening Assays, Antitumor ,ALDH1A1 gene - Abstract
Background: Small Cell Lung Cancer (SCLC) is a highly aggressive malignancy. MYC family oncogenes are amplified and overexpressed in 20% of SCLCs, showing that MYC oncogenes and MYC regulated genes are strong candidates as therapeutic targets for SCLC. c-MYC plays a fundamental role in cancer stem cell properties and malignant transformation. Several targets have been identified by the activation/repression of MYC. Deregulated expression levels of lncRNAs have also been observed in many cancers. Objective: The aim of the present study is to investigate the lncRNA profiles which depend on MYC expression levels in SCLC. Methods: Firstly, we constructed lentiviral vectors for MYC overexpression/inhibition. MYC expression is suppressed by lentiviral shRNA vector in MYC amplified H82 and N417 cells, and overexpressed by lentiviral inducible overexpression vector in MYC non-amplified H345 cells. LncRNA cDNA is transcribed from total RNA samples, and 91 lncRNAs are evaluated by qRT-PCR. Results: We observed that N417, H82 and H345 cells require MYC for their growth. Besides, MYC is not only found to regulate the expressions of genes related to invasion, stem cell properties, apoptosis and cell cycle (p21, Bcl2, cyclinD1, Sox2, Aldh1a1, and N-Cadherin), but also found to regulate lncRNAs. With this respect, expressions of AK23948, ANRIL, E2F4AS, GAS5, MEG3, H19, L1PA16, SFMBT2, ZEB2NAT, HOTAIR, Sox2OT, PVT1, and BC200 were observed to be in parallel with MYC expression, whereas expressions of Malat1, PTENP1, Neat1, UCA1, SNHG3, and SNHG6 were inversely correlated. Conclusion: Targeting MYC-regulated genes as a therapeutic strategy can be important for SCLC therapy. This study indicated the importance of identifying MYC-regulated lncRNAs and that these can be utilized to develop a therapeutic strategy for SCLC.
- Published
- 2020