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.
Concomitant targeting of the mTOR/MAPK pathways: novel therapeutic strategy in subsets of RICTOR/KRAS-altered non-small cell lung cancer
