lncRNAs as Potential Targets in Small Cell Lung Cancer: MYC -dependent Regulation

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.

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Synergistic Roles of Curcumin in Sensitising the Cisplatin Effect on a Cancer Stem Cell-Like Population Derived from Non-Small Cell Lung Cancer Cell Lines

Molecules ◽

10.3390/molecules26041056 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1056 ◽

Cited By ~ 1

Author(s):

Nazilah Abdul Satar ◽

Mohd Nazri Ismail ◽

Badrul Hisham Yahaya

Keyword(s):

Lung Cancer ◽

Stem Cell ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cellular Proliferation ◽

Combined Treatment ◽

Small Cell ◽

Cytotoxic Agents ◽

Small Cell Lung ◽

Proliferation Activity

Cancer stem cells (CSCs) represent a small subpopulation within a tumour. These cells possess stem cell-like properties but also initiate resistance to cytotoxic agents, which contributes to cancer relapse. Natural compounds such as curcumin that contain high amounts of polyphenols can have a chemosensitivity effect that sensitises CSCs to cytotoxic agents such as cisplatin. This study was designed to investigate the efficacy of curcumin as a chemo-sensitiser in CSCs subpopulation of non-small cell lung cancer (NSCLC) using the lung cancer adenocarcinoma human alveolar basal epithelial cells A549 and H2170. The ability of curcumin to sensitise lung CSCs to cisplatin was determined by evaluating stemness characteristics, including proliferation activity, colony formation, and spheroid formation of cells treated with curcumin alone, cisplatin alone, or the combination of both at 24, 48, and 72 h. The mRNA level of genes involved in stemness was analysed using quantitative real-time polymerase chain reaction. Liquid chromatography-mass spectrometry was used to evaluate the effect of curcumin on the CSC niche. A combined treatment of A549 subpopulations with curcumin reduced cellular proliferation activity at all time points. Curcumin significantly (p < 0.001) suppressed colonies formation by 50% and shrank the spheroids in CSC subpopulations, indicating inhibition of their self-renewal capability. This effect also was manifested by the down-regulation of SOX2, NANOG, and KLF4. Curcumin also regulated the niche of CSCs by inhibiting chemoresistance proteins, aldehyde dehydrogenase, metastasis, angiogenesis, and proliferation of cancer-related proteins. These results show the potential of using curcumin as a therapeutic approach for targeting CSC subpopulations in non-small cell lung cancer.

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Long noncoding RNA MCF2L‐AS1 promotes the cancer stem cell‐like traits in non‐small cell lung cancer cells through regulating miR ‐873‐5p level

Environmental Toxicology ◽

10.1002/tox.23142 ◽

2021 ◽

Author(s):

Shouguo Li ◽

Liancheng Lin

Keyword(s):

Lung Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Small Cell Lung Cancer ◽

Cancer Cells ◽

Cell Lung Cancer ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Small Cell ◽

Small Cell Lung

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Ipilimumab in non-small cell lung cancer and small-cell lung cancer: new knowledge on a new therapeutic strategy

Expert Opinion on Biological Therapy ◽

10.1517/14712598.2014.907786 ◽

2014 ◽

Vol 14 (7) ◽

pp. 1007-1017 ◽

Cited By ~ 5

Author(s):

Erika Rijavec ◽

Carlo Genova ◽

Giulia Barletta ◽

Giovanni Burrafato ◽

Federica Biello ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Therapeutic Strategy ◽

Small Cell ◽

Small Cell Lung ◽

New Knowledge

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Therapeutic strategy for postoperative recurrence in patients with non-small cell lung cancer

World Journal of Clinical Oncology ◽

10.5306/wjco.v5.i5.1048 ◽

2014 ◽

Vol 5 (5) ◽

pp. 1048 ◽

Cited By ~ 30

Author(s):

Tokujiro Yano

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Therapeutic Strategy ◽

Postoperative Recurrence ◽

Small Cell ◽

Small Cell Lung

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Using stem cell biology to design precision medicine for non-small cell lung cancer

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2015.12.006 ◽

2016 ◽

Vol 11 (2) ◽

pp. S4-S5

Author(s):

Christine M. Fillmore ◽

Chunxiao Xu ◽

Francisco J. Sánchez-Rivera ◽

Tyler Jacks ◽

Kwok-Kin Wong ◽

...

Keyword(s):

Lung Cancer ◽

Stem Cell ◽

Small Cell Lung Cancer ◽

Precision Medicine ◽

Cell Lung Cancer ◽

Cell Biology ◽

Small Cell ◽

Stem Cell Biology ◽

Small Cell Lung

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Identification of LOC338963 and AP3B2 as Potential Biomarkers for Lambert-Eaton Myasthenic Syndrome

10.21203/rs.3.rs-332560/v1 ◽

2021 ◽

Author(s):

Fei Yang ◽

Feng Jing ◽

Yang Li ◽

Shanshan Kong ◽

Shimin Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Expression Profiles ◽

Small Cell ◽

Differentially Expressed ◽

Healthy Controls ◽

Small Cell Lung ◽

Qrt Pcr ◽

Myasthenic Syndrome

Abstract Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder associated with muscle weakness and small-cell lung cancer. Here, we used microarray analysis to identify long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) that might serve as biomarkers for LEMS.Methods: Plasma lncRNA and mRNA expression profiles of three patients with paraneoplastic LEMS and three healthy controls were analyzed using Arraystar Human lncRNA Microarray v4.0. Differentially expressed lncRNAs and adjacent mRNAs were analyzed jointly, and candidates were verified in individual samples by quantitative real-time polymerase chain reaction (qRT-PCR). The identified lncRNAs and mRNAs were evaluated in nine patients with paraneoplastic LEMS, eight patients with non-tumor LEMS, and four patients with small cell lung cancer (SCLC). Results: A total of 320 lncRNAs were differentially expressed in patients with paraneoplastic LEMS compared to healthy controls (fold change >1.5, P < 0.05), and nine were further evaluated. One of the identified lncRNAS, LOC338963 (NR_031439), is known to regulated the expression of the mRNA AP3B2, and both were upregulated more than 2-fold in patients with paraneoplastic LEMS compared to healthy controls. Furthermore, qRT-PCR analysis revealed significant upregulation of LOC338963 (NR_031439) and AP3B2 expression in patients with paraneoplastic LEMS compared to those with either non-tumor LEMS (2.37- and 5.06-fold, respectively) or SCLC (4.36- and 14.97-fold, respectively).Conclusions: Plasma LOC338963 (NR_031439) and AP3B2 were found to be upregulated in LEMS and might be used as diagnostic biomarkers for this disease.

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Cancer Stem Cell Biomarkers in EGFR-Mutation–Positive Non–Small-Cell Lung Cancer

Clinical Lung Cancer ◽

10.1016/j.cllc.2019.02.005 ◽

2019 ◽

Vol 20 (3) ◽

pp. 167-177 ◽

Cited By ~ 5

Author(s):

Jordi Codony-Servat ◽

Carles Codony-Servat ◽

Andrés Felipe Cardona ◽

Ana Giménez-Capitán ◽

Ana Drozdowskyj ◽

...

Keyword(s):

Lung Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Small Cell ◽

Small Cell Lung

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TAK-243 Combined With Radiation And Other DNA Damaging Agents As A Novel Therapeutic Strategy For Small Cell Lung Cancer

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2020.07.1605 ◽

2020 ◽

Vol 108 (3) ◽

pp. e510

Author(s):

S. Majeed ◽

M. Aparnathi ◽

L. Song ◽

J. Weiss ◽

A. Schimmer ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Therapeutic Strategy ◽

Small Cell ◽

Small Cell Lung ◽

Dna Damaging Agents ◽

Novel Therapeutic

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Circ_MDM2_000139, Circ_ATF2_001418, Circ_CDC25C_002079, and Circ_BIRC6_001271 Are Involved in the Functions of XAV939 in Non-Small Cell Lung Cancer

Canadian Respiratory Journal ◽

10.1155/2019/9107806 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Haixiang Yu ◽

Lei Xu ◽

Zhengjia Liu ◽

Bo Guo ◽

Zhifeng Han ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Regulatory Network ◽

Family Members ◽

Enrichment Analysis ◽

Small Cell ◽

Small Cell Lung ◽

Expression Levels ◽

Relative Expression

Background. The small molecule inhibitor XAV939 could inhibit the proliferation and promote the apoptosis of non-small cell lung cancer (NSCLC) cells. This study was conducted to identify the key circular RNAs (circRNAs) and microRNAs (miRNAs) in XAV939-treated NSCLC cells. Methods. After grouping, the NCL-H1299 cells in the treatment group were treated by 10 μM XAV939 for 12 h. RNA-sequencing was performed, and then the differentially expressed circRNAs (DE-circRNAs) were analyzed by the edgeR package. Using the clusterprofiler package, enrichment analysis for the hosting genes of the DE-circRNAs was performed. Using Cytoscape software, the miRNA-circRNA regulatory network was built for the disease-associated miRNAs and the DE-circRNAs. The DE-circRNAs that could translate into proteins were predicted using circBank database and IRESfinder tool. Finally, the transcription factor (TF)-circRNA regulatory network was built by Cytoscape software. In addition, A549 and HCC-827 cell treatment with XAV939 were used to verify the relative expression levels of key DE-circRNAs. Results. There were 106 DE-circRNAs (including 61 upregulated circRNAs and 45 downregulated circRNAs) between treatment and control groups. Enrichment analysis for the hosting genes of the DE-circRNAs showed that ATF2 was enriched in the TNF signaling pathway. Disease association analysis indicated that 8 circRNAs (including circ_MDM2_000139, circ_ATF2_001418, circ_CDC25C_002079, and circ_BIRC6_001271) were correlated with NSCLC. In the miRNA-circRNA regulatory network, let-7 family members⟶circ_MDM2_000139, miR-16-5p/miR-134-5p⟶circ_ATF2_001418, miR-133b⟶circ_BIRC6_001271, and miR-221-3p/miR-222-3p⟶circ_CDC25C_002079 regulatory pairs were involved. A total of 47 DE-circRNAs could translate into proteins. Additionally, circ_MDM2_000139 was targeted by the TF POLR2A. The verification test showed that the relative expression levels of circ_MDM2_000139, circ_CDC25C_002079, circ_ATF2_001418, and circ_DICER1_000834 in A549 and HCC-827 cell treatment with XAV939 were downregulated comparing with the control. Conclusions. Let-7 family members and POLR2A targeting circ_MDM2_000139, miR-16-5p/miR-134-5p targeting circ_ATF2_001418, miR-133b targeting circ_BIRC6_001271, and miR-221-3p/miR-222-3p targeting circ_CDC25C_002079 might be related to the mechanism in the treatment of NSCLC by XAV939.

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