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lncRNAs as Potential Targets in Small Cell Lung Cancer: MYC -dependent Regulation
Onur Tokgun1,2, Pervin E Tokgun1, Kubilay Inci2
1Department of Medical Genetics, Faculty of Medicine, Pamukkale University, Denizli, Turkey
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.
Insights
This study investigated MYC-regulated long non-coding RNAs (lncRNAs) in Small Cell Lung Cancer (SCLC). Researchers found specific lncRNAs that correlate with MYC expression, offering potential new therapeutic targets for this aggressive cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Small Cell Lung Cancer (SCLC) is an aggressive malignancy with MYC oncogene amplification in 20% of cases.
- MYC oncogenes and their regulated genes are critical therapeutic targets in SCLC.
- Dysregulated long non-coding RNA (lncRNA) expression is observed in various cancers.
Purpose of the Study:
- To investigate lncRNA profiles associated with MYC expression levels in SCLC.
- To identify MYC-regulated lncRNAs as potential therapeutic targets for SCLC.
Main Methods:
- Constructed lentiviral vectors for MYC overexpression and inhibition in SCLC cell lines.
- Suppressed MYC expression using shRNA in H82 and N417 cells; overexpressed MYC in H345 cells.
- Evaluated 91 lncRNAs using qRT-PCR on total RNA samples.
Main Results:
- MYC is essential for the growth of N417, H82, and H345 SCLC cells.
- MYC regulates genes involved in invasion, stemness, apoptosis, and cell cycle.
- Identified specific lncRNAs (e.g., HOTAIR, PVT1) with expression parallel to MYC, and others (e.g., Malat1, Neat1) inversely correlated.
Conclusions:
- MYC-regulated genes are important therapeutic targets for SCLC.
- Identifying MYC-regulated lncRNAs is crucial for developing novel SCLC therapeutic strategies.
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