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 activation/repression of MYC.Deregulated expression levels of
lncRNAs have also been observed in many cancers.
Objective:
Purpose of the study is to investigate the lncRNA profiles depend on MYC expression levels in SCLC.
Methods: First, 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 obtained that N417, H82 and H345 cells are seem to be addicted to Myc for their growth. Besides, Myc is
found to regulate the expressions of genes related to invasion, stem cell properties, apoptosis and cell cycle (p21, Bcl2,
cyclinD1, Sox2, Aldh1a1, N-Cadherin) and also lncRNAs. With this respect AK23948, ANRIL, E2F4AS, GAS5, MEG3,
H19, L1PA16, SFMBT2, ZEB2NAT, HOTAIR, Sox2OT, PVT1 and BC200 expressions were in parallel with Myc
expression whereas Malat1, PTENP1, Neat1, UCA1, SNHG3 and SNHG6 expressions were inversely correlated.
Conclusion:
Targeting Myc-regulated genes as a therapeutic strategy can be important for SCLC therapy. This study has
importance for identifying Myc-regulated lncRNAs with regards to developing therapeutic strategy in SCLC.