|
|
Identify biomolecular markers and targeted drugs for pancreatic ductal adenocarcinoma based on autophagy- long non-coding RNA regulatory networks |
TANG Tianshu XU Dehua LIU Jinchan CHEN Ming CHEN Xiaolin RAO Shaoqi |
Institute for Medical Systems Biology, School of Public Health, Guangdong Medical University, Guangdong Province, Dongguan 523000, China
|
|
|
Abstract Objective To systematically explore the long non-coding RNA (lncRNA) related to the prognosis of pancreatic ductal adenocarcinoma (PDAC) as well as the potential therapeutic drugs by using public transcriptome RNA sequencing data. Methods Transcriptome (RNA-seq) and clinical data for PDAC patients were obtained from TCGA database. The autophagy-related lnc RNA(ARlncRNA) gene expressions were identified by pearson correlation analysis, than filtered by univariate Kaplan-Meier method and multivariate Cox regression analysis, the gene network regulated by these ARlncRNA was constructed. Finally, the target drugs recognitied by the protein-protein interaction network and Drug-Gene Interaction database (DGIdbs). Results A total of 12 ARlncRNA related to the prognosis of the PDAC patients, the ten coexpressed mRNA (core genes) had significant influence on the overall survival of patients. Enrichment analysis mainly provided the autophagy pathway. Network analysis and database mining identified three potential drugs for PDAC(Afatinib, Dacomitinib, and Osimertinib). Conclusion The ARlncRNA-mRNA network is established to reveal the pathogenesis of PDAC and identify molecular markers, the three potential therapeutic drugs for PDAC are identified by DGIdbs.
|
|
|
|
|
[1] Yang L,Wang H,Shen Q,et al. Long non-coding RNAs involved in autophagy regulation [J]. Cell Death Dis,2017, 2017(8):464-473.
[2] Yang S,Wang X,Contino G,et al. Pancreatic cancers require autophagy for tumor growth [J]. Genes Dev,2011,25(7):717-729.
[3] Yun CW,Lee SH. The Roles of Autophagy in Cancer [J]. Int J Mol Sci,2018,19(11):1-18.
[4] Iyer MK,Niknafs YS,Malik R,et al. The landscape of long noncoding RNAs in the human transcriptome [J]. Nature Genetics,2015,47(3):199-208.
[5] Zhou C,Yi C,Yi Y,et al. LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/β- catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes [J]. Mol Cancer,2020,19(1):118.
[6] Iacobuzio-Donahue CA,Yachida S,Jones S,et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer [J]. Nature (London),2010,467(7319):1114- 1117.
[7] Huang F,Chen W,Peng J,et al. LncRNA PVT1 triggers Cyto-protective autophagy and promotes pancreatic ductal adenocarcinoma development via the miR-20a-5p/ULK1 Axis [J]. Mol Cancer,2018,17(1):1-16.
[8] Claudia Allemani TMVD. Cancer statistics,2018 [J]. Lancet,2018,391(10125):1023-1075.
[9] Jacquin MA,Chiche J,Zunino B,et al. GAPDH binds to active Akt,leading to Bcl-xL increase and escape from caspase-independent cell death [J]. Cell Death Differ,2013,20(8):1043-1054.
[10] Ishizone S,Yamauchi K,Kawa S,et al. Clinical utility of quantitative RT-PCR targeted to alpha1,4-N-acetylglucosaminyltransferase mRNA for detection of pancreatic cancer [J]. Cancer Sci,2006,97(2):119-126.
[11] Stephan S,Datta K,Wang E,et al. Effect of Rapamycin Alone and in Combination with Antiangiogenesis Therapy in an Orthotopic Model of Human Pancreatic Cancer [J]. Clin Cancer Res,2004,10(20):6993-7000.
[12] Zhang G,Zhong J,Lin L,et al. MiR-19 enhances pancreatic cancer progression by targeting PTEN through PI3K/ AKT signaling pathway [J]. Eur Revi Med Pharmacol Sci,2020,24(3):1098-1107.
[13] Mortazavi M,Moosavi F,Martini M,et al. Prospects of targeting PI3K/AKT/mTOR pathway in pancreatic cancer[J]. Crit Rev Oncol Hematol,2022,176:103749.
[14] Pishvaian MJ,Bender RJ,Halverson D,et al. Molecular Profiling of Patients with Pancreatic Cancer: Initial Results from the Know Your Tumor Initiative [J]. Clin Cancer Res,2018,24(20):5018-5027.
[15] Azmi AS,Mohammad RM. Non-peptidic small molecule inhibitors against Bcl-2 for cancer therapy [J]. J Cell Physiol,2009,218(1):13-21.
[16] Zhan W,Hu X ,Yi J. Inhibitory activity of apogossypol in human prostate cancer in vitro and in vivo [J]. Mol Med Rep, 2015,11(6):4142-4148.
[17] Hollevoet K,Antignani A,Fitzgerald DJ,et al. Combining the antimesothelin immunotoxin SS1P with the BH3- mimetic ABT-737 induces cell death in SS1P-resistant pancreatic cancer cells [J]. J Immunother,2014,37(1):8-15.
[18] Kaushik G,Seshacharyulu P,Rauth S,et al. Selective inhibition of stemness through EGFR/FOXA2/SOX9 axis reduces pancreatic cancer metastasis [J]. Oncogene,2021,40(4):848-862.
[19] Zhu S,Zhang Q,Sun X,et al. HSPA5 Regulates Ferroptotic Cell Death in Cancer Cells [J]. Cancer Res(Chicago,Ill.),2017,77(8):2064-2077.
[20] Kumar A,Singh UK,Chaudhary A. Targeting autophagy to overcome drug resistance in cancer therapy [J]. Future Med Chem,2015,7(12):1535-1542.
[21] Chen C,Hsieh T,Lin Y,et al. Targeting Autophagy by MPT0L145,a Highly Potent PIK3C3 Inhibitor,Provides Synergistic Interaction to Targeted or Chemotherapeutic Agents in Cancer Cells [J]. Cancers,2019,11(9):1345.
[22] Miao CC,Hwang W,Chu LY,et al. LC3A-mediated autop- hagy regulates lung cancer cell plasticity [J]. Autophagy,2022,18(4):921-934.
[23] Tekirdag KA,Cuervo AM. Chaperone-mediated autophagy and endosomal microautophagy: Jointed by a chaperone[J]. Biol Chem,2018,293(15):5414- 5424.
[24] Tanaka M,Mun S,Harada A,et al. Hsc70 contributes to cancer cell survival by preventing Rab1A degradation under stress conditions [J]. PLoS One,2014,9(5):e96785.
[25] Hirsh V. Afatinib (BIBW 2992) development in non-small- cell lung cancer [J]. Future Oncology,2011,7(7):817-825.
[26] Engelman JA,Zejnullahu K,Gale CM,et al. PF00299804,an irreversible pan-ERBB inhibitor,is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib [J]. Cancer Res,2007,67(24):11924- 11932.
[27] Mok TS,Wu Y-L,Ahn M-J,et al. Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer [J]. N Engl J Med,2017,376(7):629-640. |
|
|
|