Research Article

Integrated Analysis of mRNA-seq and miRNA-seq to Identify c-MYC, YAP1 and miR-3960 as Major Players in the Anticancer Effects of Caffeic Acid Phenethyl Ester in Human Small Cell Lung Cancer Cell Line

Author(s): Fei Mo, Ya Luo, Dian Fan, Hao Zeng, Yunuo Zhao, Meng Luo, Xiaobei Liu and Xuelei Ma*

Volume 20, Issue 1, 2020

Page: [15 - 24] Pages: 10

DOI: 10.2174/1566523220666200523165159

Price: $65

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Abstract

Background: Caffeic Acid Phenethyl Ester (CAPE), an active extract of propolis, has recently been reported to have broad applications in various cancers. However, the effects of CAPE on Small Cell Lung Cancer (SCLC) are largely unknown. Therefore, the aim of this study was to determine the anti-proliferative effect of CAPE and explore the underlying molecular mechanisms in SCLC cells using high-throughput sequencing and bioinformatics analysis.

Methods: Small-cell lung cancer H446 cells were treated with CAPE, and cell proliferation and apoptosis were then assessed. Additionally, the regulation mediated by miR-3960 after CAPE treatment was explored and the altered signaling pathways were predicted in a bioinformatics analysis.

Results: CAPE significantly inhibited cell proliferation and induced apoptosis. CAPE decreased the expression of Yes-Associated Protein 1 (YAP1) and cellular myelocytomatosis oncogene (c-MYC) protein. Moreover, the upregulation of miR-3960 by CAPE contributed to CAPE-induced apoptosis. The knockdown of miR-3960 decreased the CAPE-induced apoptosis.

Conclusion: We demonstrated the anti-cancer effect of CAPE in human SCLC cells and studied the mechanism by acquiring a comprehensive transcriptome profile of CAPE-treated cells.

Keywords: Caffeic acid phenethyl ester, small cell lung cancer, miR-3960, c-MYC, YAP1, high-throughput sequencing.

Graphical Abstract
[1]
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(2): 87-108.
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[2]
Gkountakos A, Sartori G, Falcone I, et al. PTEN in lung cancer: Dealing with the problem, building on new knowledge and turning the game around. Cancers (Basel) 2019; 11(8): 1141-60.
[http://dx.doi.org/10.3390/cancers11081141] [PMID: 31404976]
[3]
Tie Y, Zheng H, He Z, et al. Targeting folate receptor β positive tumor-associated macrophages in lung cancer with a folate-modified liposomal complex. Signal Transduct Target Ther 2020; 5(1): 6.
[http://dx.doi.org/10.1038/s41392-020-0115-0] [PMID: 31993222]
[4]
Song Y, Liu P, Huang Y, Guan Y, Han X, Shi Y. Osimertinib quantitative and gene variation analyses in cerebrospinal fluid and plasma of a non-small cell lung cancer patient with leptomeningeal metastases. Curr Cancer Drug Targets 2019; 19(8): 666-73.
[http://dx.doi.org/10.2174/1568009618666181017114111] [PMID: 30332963]
[5]
Ma CC, Wang ZL, Xu T, He ZY, Wei YQ. The approved gene therapy drugs worldwide: from 1998 to 2019. Biotechnol Adv 2020; 40: 107502
[http://dx.doi.org/10.1016/j.biotechadv.2019.107502] [PMID: 31887345]
[6]
Pešek M, Mužík J. [Small-cell lung cancer: epidemiology, diagnostics and therapy]. Vnitr Lek 2018; 63(11): 876-83.
[PMID: 29303289]
[7]
Miller KD, Nogueira L, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin 2019; 69(5): 363-85.
[http://dx.doi.org/10.3322/caac.21565] [PMID: 31184787]
[8]
Esposito S, Bianco A, Russo R, Di Maro A, Isernia C, Pedone PV. Therapeutic perspectives of molecules from urtica dioica extracts for cancer treatment. Molecules 2019; 24(15): 2753.
[http://dx.doi.org/10.3390/molecules24152753] [PMID: 31362429]
[9]
Mileo AM, Nisticò P, Miccadei S. Polyphenols: Immunomodulatory and therapeutic implication in colorectal cancer. Front Immunol 2019; 10: 729.
[http://dx.doi.org/10.3389/fimmu.2019.00729] [PMID: 31031748]
[10]
Chen CY, Kao CL, Liu CM. The cancer prevention, anti-inflammatory and anti-oxidation of bioactive phytochemicals targeting the tlr4 signaling pathway. Int J Mol Sci 2018; 19(9): 2729.
[http://dx.doi.org/10.3390/ijms19092729] [PMID: 30213077]
[11]
Budisan L, Gulei D, Zanoaga OM, et al. Dietary intervention by phytochemicals and their role in modulating coding and non-coding genes in cancer. Int J Mol Sci 2017; 18(6): 1178.
[http://dx.doi.org/10.3390/ijms18061178] [PMID: 28587155]
[12]
Anjaly K, Tiku AB. Radio-Modulatory potential of caffeic acid phenethyl ester: A therapeutic perspective. Anticancer Agents Med Chem 2018; 18(4): 468-75.
[http://dx.doi.org/10.2174/1871520617666171113143945] [PMID: 29141565]
[13]
Budisan L, Gulei D, Jurj A, et al. Inhibitory effect of cape and kaempferol in colon cancer cell lines-possible implications in new therapeutic strategies. Int J Mol Sci 2019; 20(5): 1199.
[http://dx.doi.org/10.3390/ijms20051199] [PMID: 30857282]
[14]
Fraser SP, Hemsley F, Djamgoz MBA. Caffeic acid phenethyl ester: Inhibition of metastatic cell behaviours via voltage-gated sodium channel in human breast cancer in vitro. Int J Biochem Cell Biol 2016; 71: 111-8.
[http://dx.doi.org/10.1016/j.biocel.2015.12.012] [PMID: 26724521]
[15]
Abente EJ, Subramanian M, Ramachandran V, Najafi-Shoushtari SH. MicroRNAs in obesity-associated disorders. Arch Biochem Biophys 2016; 589: 108-19.
[http://dx.doi.org/10.1016/j.abb.2015.09.018] [PMID: 26416722]
[16]
Silvestro S, Bramanti P, Mazzon E. Role of MiRNAs in alzheimer’s disease and possible fields of application. Int J Mol Sci 2019; 20(16): 3979.
[http://dx.doi.org/10.3390/ijms20163979] [PMID: 31443326]
[17]
Flórez CAR, García-Perdomo HA, Escudero MM. MicroRNAs associated with overweight and obesity in childhood. Systematic review. MicroRNA 2019; 9(4): 1-11.
[http://dx.doi.org/10.2174/2211536609666191209152721] [PMID: 31814558]
[18]
Orso F, Quirico L, Dettori D, et al. Role of miRNAs in tumor and endothelial cell interactions during tumor progression. Semin Cancer Biol 2019; 60: 214-24.
[http://dx.doi.org/10.1016/j.semcancer.2019.07.024] [PMID: 31386907]
[19]
Karamitopoulou E, Haemmig S, Baumgartner U, Schlup C, Wartenberg M, Vassella E. MicroRNA dysregulation in the tumor microenvironment influences the phenotype of pancreatic cancer. Mod Pathol 2017; 30(8): 1116-25.
[http://dx.doi.org/10.1038/modpathol.2017.35] [PMID: 28548126]
[20]
Babu N, Advani J, Solanki HS, et al. miRNA and proteomic dysregulation in non-small cell lung cancer in response to cigarette smoke. MicroRNA 2018; 7(1): 38-53.
[http://dx.doi.org/10.2174/2211536607666180103165343] [PMID: 29299995]
[21]
Akgun S, Kucuksayan H, Ozes ON, et al. NF-κB-Induced Upregulation of miR-548as-3p Increases Invasion of NSCLC by Targeting PTEN. Anticancer Agents Med Chem 2019; 19(8): 1058-68.
[http://dx.doi.org/10.2174/1871520619666190206165215] [PMID: 30727918]
[22]
Bhardwaj V, Mandal AKA. Next-Generation sequencing reveals the role of Epigallocatechin-3-Gallate in regulating putative novel and known microRNAs which target the MAPK pathway in non-small-cell lung cancer A549 Cells. Molecules 2019; 24(2): 368.
[http://dx.doi.org/10.3390/molecules24020368] [PMID: 30669618]
[23]
Tripathi P, Singh J, Lal JA, Tripathi V. Next-Generation sequencing: An emerging tool for drug designing. Curr Pharm Des 2019; 25(31): 3350-7.
[http://dx.doi.org/10.2174/1381612825666190911155508] [PMID: 31544713]
[24]
Kavitha N, Vijayarathna S, Shanmugapriya , et al. MicroRNA profiling in MDA-MB-231 human breast cancer cell exposed to the Phaleria macrocarpa (Boerl.) fruit ethyl acetate fraction (PMEAF) through IIlumina Hi-Seq technologies and various in silico bioinformatics tools. J Ethnopharmacol 2018; 213: 118-31.
[http://dx.doi.org/10.1016/j.jep.2017.11.009] [PMID: 29154802]
[25]
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 2014; 15(12): 550.
[http://dx.doi.org/10.1186/s13059-014-0550-8] [PMID: 25516281]
[26]
Ashburner M, Ball CA, Blake JA, et al. The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat Genet 2000; 25(1): 25-9.
[http://dx.doi.org/10.1038/75556] [PMID: 10802651]
[27]
Ai C, Kong L. CGPS: A machine learning-based approach integrating multiple gene set analysis tools for better prioritization of biologically relevant pathways. J Genet Genomics 2018; 45(9): 489-504.
[http://dx.doi.org/10.1016/j.jgg.2018.08.002] [PMID: 30292791]
[28]
Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods 2012; 9(4): 357-9.
[http://dx.doi.org/10.1038/nmeth.1923] [PMID: 22388286]
[29]
Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. eLife 2015., 4e05005
[http://dx.doi.org/10.7554/eLife.05005] [PMID: 26267216]
[30]
Shen J, Cao S, Sun X, et al. Sinoporphyrin Sodium-Mediated Sonodynamic therapy inhibits RIP3 Expression and induces apoptosis in the H446 small cell lung cancer cell line. Cell Physiol Biochem 2018; 51(6): 2938-54.
[http://dx.doi.org/10.1159/000496045] [PMID: 30562734]
[31]
Goan YG, Wu WT, Liu CI, Neoh CA, Wu YJ. Involvement of mitochondrial dysfunction, endoplasmic reticulum stress, and the PI3K/AKT/mTOR pathway in Nobiletin-Induced apoptosis of human bladder cancer cells. Molecules 2019; 24(16): 2881.
[http://dx.doi.org/10.3390/molecules24162881] [PMID: 31398899]
[32]
Fontes A, Alemany-Pagès M, Oliveira PJ, Ramalho-Santos J, Zischka H, Azul AM. Antioxidant versus pro-apoptotic effects of mushroom-enriched diets on mitochondria in liver disease. Int J Mol Sci 2019; 20(16): 3987.
[http://dx.doi.org/10.3390/ijms20163987] [PMID: 31426291]
[33]
Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120(1): 15-20.
[http://dx.doi.org/10.1016/j.cell.2004.12.035] [PMID: 15652477]
[34]
Shen X, Liu Y, Luo X, Yang Z. Advances in biosynthesis, pharmacology, and pharmacokinetics of pinocembrin, a promising natural small-molecule drug. Molecules 2019; 24(12): 2323.
[http://dx.doi.org/10.3390/molecules24122323] [PMID: 31238565]
[35]
Liang Y, Feng G, Wu L, et al. Caffeic acid phenethyl ester suppressed growth and metastasis of nasopharyngeal carcinoma cells by inactivating the NF-κB pathway. Drug Des Devel Ther 2019; 13: 1335-45.
[http://dx.doi.org/10.2147/DDDT.S199182] [PMID: 31118570]
[36]
Shin EJ, Jo S, Choi HK, Choi S, Byun S, Lim TG. Caffeic acid phenethyl ester inhibits UV-Induced MMP-1 expression by targeting histone acetyltransferases in human skin. Int J Mol Sci 2019; 20(12): 3055.
[http://dx.doi.org/10.3390/ijms20123055] [PMID: 31234539]
[37]
Sorrenti V, Raffaele M, Vanella L, et al. Protective effects of Caffeic Acid Phenethyl Ester (CAPE) and novel cape analogue as inducers of Heme Oxygenase-1 in Streptozotocin-Induced Type 1 diabetic rats. Int J Mol Sci 2019; 20(10): 2441.
[http://dx.doi.org/10.3390/ijms20102441] [PMID: 31108850]
[38]
Li Y, Zhang X, Zhou X, Zhang X. LHPP suppresses bladder cancer cell proliferation and growth via inactivating AKT/p65 signaling pathway. Biosci Rep 2019; 39(7): BSR20182270
[http://dx.doi.org/10.1042/BSR20182270] [PMID: 31262971]
[39]
Cembrowski MS. Single-cell transcriptomics as a framework and roadmap for understanding the brain. J Neurosci Methods 2019; 326: 108353
[http://dx.doi.org/10.1016/j.jneumeth.2019.108353] [PMID: 31351971]
[40]
Dasgupta K, Chung JU, Asam K, Jeong J. Molecular patterning of the embryonic cranial mesenchyme revealed by genome-wide transcriptional profiling. Dev Biol 2019; 455(2): 434-48.
[http://dx.doi.org/10.1016/j.ydbio.2019.07.015] [PMID: 31351040]
[41]
Gaebler C, Lorenzi JCC, Oliveira TY, et al. Combination of quadruplex qPCR and next-generation sequencing for qualitative and quantitative analysis of the HIV-1 latent reservoir. J Exp Med 2019; 216(10): 2253-64.
[http://dx.doi.org/10.1084/jem.20190896] [PMID: 31350309]
[42]
Pant N, Rakshit S, Paul S, Saha I. Genome-wide analysis of multi-view data of miRNA-seq to identify miRNA biomarkers for stomach cancer. J Biomed Inform 2019; 97: 103254
[http://dx.doi.org/10.1016/j.jbi.2019.103254] [PMID: 31352060]
[43]
Chiu CM, Lin FM, Chang TH, et al. Clinical detection of human probiotics and human pathogenic bacteria by using a novel high-throughput platform based on next generation sequencing. J Clin Bioinforma 2014; 4(1): 1.
[http://dx.doi.org/10.1186/2043-9113-4-1] [PMID: 24418497]
[44]
Renaud L, da Silveira WA, Glen WB Jr, Hazard ES, Hardiman G. and Interplay Between MicroRNAs and Targeted Genes in Cellular Homeostasis of Adult Zebrafish (Danio rerio). Curr Genomics 2018; 19(7): 615-29.
[http://dx.doi.org/10.2174/1389202919666180503124522] [PMID: 30386173]
[45]
Bibi N, Niaz H, Hupp T, Kamal MA, Rashid S. Screening and identification of PLK1-Polo box binding peptides by high-throughput sequencing of phage-selected libraries. Protein Pept Lett 2019; 26(8): 620-33.
[http://dx.doi.org/10.2174/0929866526666190318101054] [PMID: 30887917]
[46]
Liu Q, Peng F, Chen J. The role of exosomal MicroRNAs in the tumor microenvironment of breast cancer. Int J Mol Sci 2019; 20(16): 3884.
[http://dx.doi.org/10.3390/ijms20163884] [PMID: 31395836]
[47]
Kang M, Lee KH, Lee HS, et al. Concurrent treatment with simvastatin and NF-κB inhibitor in human castration-resistant prostate cancer cells exerts synergistic anti-cancer effects via control of the NF-κB/LIN28/let-7 miRNA signaling pathway. PLoS One 2017; 12(9): e0184644
[http://dx.doi.org/10.1371/journal.pone.0184644] [PMID: 28910332]
[48]
Huang D, Huang Y, Huang Z, Weng J, Zhang S, Gu W. Relation of AURKB over-expression to low survival rate in BCRA and reversine-modulated aurora B kinase in breast cancer cell lines. Cancer Cell Int 2019; 19: 166.
[http://dx.doi.org/10.1186/s12935-019-0885-z] [PMID: 31244554]
[49]
Hu Y, Xu R, Chen CY, et al. Extracellular vesicles from human umbilical cord blood ameliorate bone loss in senile osteoporotic mice. Metabolism 2019; 95: 93-101.
[http://dx.doi.org/10.1016/j.metabol.2019.01.009] [PMID: 30668962]
[50]
Wu F, Xing T, Gao X, Liu F. miR‑501‑3p promotes colorectal cancer progression via activation of Wnt/β‑catenin signaling. Int J Oncol 2019; 55(3): 671-83.
[http://dx.doi.org/10.3892/ijo.2019.4852] [PMID: 31364752]
[51]
Yang Y, Xue K, Li Z, et al. c-Myc regulates the CDK1/cyclin B1 dependent‑G2/M cell cycle progression by histone H4 acetylation in Raji cells. Int J Mol Med 2018; 41(6): 3366-78.
[http://dx.doi.org/10.3892/ijmm.2018.3519] [PMID: 29512702]
[52]
Kim SH, Jin H, Meng RY, et al. Activating hippo pathway via Rassf1 by ursolic acid suppresses the tumorigenesis of gastric cancer. Int J Mol Sci 2019; 20(19): 4709.
[http://dx.doi.org/10.3390/ijms20194709] [PMID: 31547587]
[53]
Kang W, Tong JH, Chan AW, et al. Yes-associated protein 1 exhibits oncogenic property in gastric cancer and its nuclear accumulation associates with poor prognosis. Clin Cancer Res 2011; 17(8): 2130-9.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2467] [PMID: 21346147]

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