Identification and validation of a five-lncRNA signature for predicting survival with targeted drug candidates in ovarian cancer

被引：25
作者：
Lin, Nuan [1 ,2 ,3 ,4 ]
Lin, Jia-zhe [5 ]
Tanaka, Yoshiaki [6 ]
Sun, Pingnan [2 ,3 ,4 ]
Zhou, Xiaoling [2 ,3 ,4 ]
机构：
[1] Shantou Univ, Affiliated Hosp 1, Obstet & Gynecol Dept, Med Coll, Shantou, Peoples R China
[2] Shantou Univ, Stem Cell Res Ctr, Med Coll, Shantou, Peoples R China
[3] Shantou Univ, Ctr Reprod Med, Med Coll, Shantou, Peoples R China
[4] Shantou Univ, Guangdong Prov Key Lab Infect Dis & Mol Immunopat, Med Coll, Shantou, Peoples R China
[5] Shantou Univ, Affiliated Hosp 1, Med Coll, Neurosurg Dept, Shantou, Peoples R China
[6] Yale Sch Med, Yale Stem Cell Ctr, Dept Genet, New Haven, CT USA
来源：
BIOENGINEERED | 2021年 / 12卷 / 01期
基金：
中国国家自然科学基金;
关键词：
Ovarian cancer; risk signature; long non-coding rnas; small molecular drugs; computational biology; NONCODING RNAS; MICRORNAS; GROWTH; GENE; TRIFLUOPERAZINE; ANGIOGENESIS; INHIBITION; LOPERAMIDE; APOPTOSIS; NETWORKS;
D O I：
10.1080/21655979.2021.1946632
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
The dysregulation of long non-coding RNAs (lncRNAs) plays a crucial role in ovarian cancer (OC). In this study, we screened out five differentially expressed lncRNAs (AC092718.4, AC138035.1, BMPR1B-DT, RNF157-AS1, and TPT1-AS1) between OC and normal ovarian based on TCGA and GTEx RNA-seq databases by using Kaplan-Meier analysis and univariate Cox, LASSO, and multivariate Cox regression. Then, a risk signature was constructed, with 1, 3, 5-year survival prediction accuracy confirmed by ROC curves, and an online survival calculator for easier clinical use. With lncRNA-microRNA-mRNA regulatory networks established, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, suggesting the involvement of a variety of cancer-related functions and pathways. Finally, five candidate small-molecule drugs (thioridazine, trifluoperazine, loperamide, LY294002, and puromycin) were predicted by Connectivity Map. In conclusion, we identified a 5-lncRNA signature of prognostic value with its ceRNA networks, and five candidate drugs against OC. [GRAPHICS]
引用
收藏
页码：3263 / 3274
页数：12
相关论文
共 46 条
[1]   Predicting effective microRNA target sites in mammalian mRNAs [J].
Agarwal, Vikram ;
Bell, George W. ;
Nam, Jin-Wu ;
Bartel, David P. .
ELIFE, 2015, 4
[2]   Non-coding RNA networks in cancer [J].
Anastasiadou, Eleni ;
Jacob, Leni S. ;
Slack, Frank J. .
NATURE REVIEWS CANCER, 2018, 18 (01) :5-18
[3]  
[Anonymous], 2015, Modelling Survival Data in Medical Research
[4]  
[Anonymous], 2004, Cochrane Database Syst. Rev
[5]   Patterns of Mullerian Inhibiting Substance Type II and Candidate Type I Receptors in Epithelial Ovarian Cancer [J].
Basal, E. ;
Ayeni, T. ;
Zhang, Q. ;
Langstraat, C. ;
Donahoe, P. K. ;
Pepin, D. ;
Yin, X. ;
Leof, E. ;
Cliby, W. .
CURRENT MOLECULAR MEDICINE, 2016, 16 (03) :222-231
[6]   Targeting Insulin and Insulin-Like Growth Factor Pathways in Epithelial Ovarian Cancer [J].
Beauchamp, Marie-Claude ;
Yasmeen, Amber ;
Knafo, Ariane ;
Gotlieb, Walter H. .
JOURNAL OF ONCOLOGY, 2010, 2010
[7]   miRDB: an online database for prediction of functional microRNA targets [J].
Chen, Yuhao ;
Wang, Xiaowei .
NUCLEIC ACIDS RESEARCH, 2020, 48 (D1) :D127-D131
[8]   A paradigm shift in medicine: A comprehensive review of network-based approaches [J].
Conte, Federica ;
Fiscon, Giulia ;
Licursi, Valerio ;
Bizzarri, Daniele ;
D'Anto, Tommaso ;
Farina, Lorenzo ;
Paci, Paola .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2020, 1863 (06)
[9]   Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer [J].
Conte, Federica ;
Fiscon, Giulia ;
Chiara, Matteo ;
Colombo, Teresa ;
Farina, Lorenzo ;
Paci, Paola .
PLOS ONE, 2017, 12 (02)
[10]   PARP inhibitors in ovarian cancer [J].
Franzese, Elisena ;
Centonze, Sara ;
Diana, Anna ;
Carlino, Francesca ;
Guerrera, Luigi Pio ;
Di Napoli, Marilena ;
De Vita, Ferdinando ;
Pignata, Sandro ;
Ciardiello, Fortunato ;
Orditura, Michele .
CANCER TREATMENT REVIEWS, 2019, 73 :1-9
12345