Abstract
NoncoRNA (http://www.ncdtcdb.cn:8080/NoncoRNA/) is a manually curated database of experimentally supported non-coding RNAs (ncRNAs) and drug target associations that aim to potentially provide a high-quality data resource for exploring drug sensitivity/resistance-related ncRNAs in various human cancers. ncRNA are RNA molecular that do not encode proteins, but are involved in gene regulation and cellular functions in variety of human diseases, including neurodegenerative diseases and cancers. Here, we developed NoncoRNA which contained 8233 entries between 5568 ncRNAs and 154 drugs in 134 cancers. Each entry in the NoncoRNA contains detailed information on the ncRNAs, drugs, and cancers, the ncRNA expression pattern and experimental detection techniques, drug response and other targets, literature references, and other information. NoncoRNA offers a user-friendly, open access web interface to easily browse, search, and download data. NoncoRNA also provides a submission page for researchers to submit newly validated ncRNA-drug-cancer associations. NoncoRNA might serve as an immeasurable resource for understanding the roles of ncRNAs in cancer therapy.
Keywords: Database, Non-coding RNA, Drug resistance, Human cancer
To the Editor,
Cancer is an important cause of morbidity and mortality worldwide, in every world region, and irrespective of the level of human development [1]. In addition, the incidence and mortality of cancer have increased rapidly worldwide in recent years. The reasons are complex, but drug resistance is the primary cause of clinical treatment failure [2]. However, the mechanism of drug resistance to chemotherapeutic agents is not fully elucidated. Currently, more and more evidences have been proved that non-coding RNAs play critical roles in drug resistance [3–6]. ncRNAs including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), and PIWI-interacting RNAs (piRNAs) are suggested to be the potential promising therapeutic targets for overcoming drug resistance in the treatment of human cancers [7–10]. Due to their functional importance, ncRNAs are under intense study at present, and some databases have been built to describe ncRNAs’ functional characterization, such as ncDR, Lnc2Cancer, SM2miR, CircR2Disease, and piRBase. Current ncRNA research related to drug resistance is mainly focused on lncRNAs and miRNAs. However, few studies have reported the association between circRNAs and piRNAs. Therefore, it is urgent demand to establish a database for more comprehensive data coverage drug resistance and ncRNAs in human cancers.
To fill this gap, we introduced NoncoRNA, a manually curated database of experimentally supported non-coding RNA and drug target associations in cancers. The current version contains 8233 entries involved in 5568 ncRNAs and 154 drugs in 134 cancers (Table 1). In addition, we also summarized the key ncRNAs of most common 10 drugs and the cancers associated ncRNAs in Additional file 1: Table S1 and S2.
Table 1.
Data summary in NoncoRNA database
| Features | NoncoRNA |
|---|---|
| Entries | 8233 |
| LncRNAs | 3599 |
| miRNAs | 1006 |
| circRNAs | 959 |
| piRNAs | 4 |
| Cancer subtypes | 134 |
| Drugs | 154 |
| Target gene | 721 |
| Pathways | 340 |
| Articles | 1615 |
To establish a high-quality database of ncRNAs, all the articles related to drug resistance and ncRNAs were manually extracted from publications (Fig. 1). (i) We searched all published studies in the PubMed database using the following combination of keywords: “long non-coding RNA or lncRNA and drug and cancer,” “microRNA or miRNA and drug and cancer,” “circRNA and drug and cancer,” and “piRNA or PIWI-interacting RNA and drug and cancer.” Besides, we also integrated relevant information from ncDR and Lnc2Cancer. Then, we manually retrieved entries related to ncRNAs, drugs, and cancers by reading abstracts. (ii) The abstract and the full text of selected articles were manually screened to extract drug resistance-related ncRNAs and their detailed annotation information, such as article’s basic information, ncRNAs’ basic information, drug basic information, and the relationship between ncRNAs and drugs. The relationship between ncRNAs and drugs in cancers were supported by experiment, such as qRT-PCR, southern-blot, and high-throughput experiment. Similarly, we have provided experimental data related to ncRNAs and drug resistance in our laboratory, such as lnc-ERC1-1:5, lnc-SCG3-3:3, and NR_028415. (iii) In order to share information among different databases, we unified the information by certain criteria, including the drug ID from DrugBank and ncRNA ID from Ensembl, miRBase, circBase, piRBase, and so on. Then Disease Ontology and DrugBank were used to respectively unify cancer and drug annotations.
Fig. 1.
The workflow of the construction of NoncoRNA database
NoncoRNA offers a user-friendly, open access web interface to easily browse, search, and download data. Figure 1 shows the schematic workflow of NoncoRNA database. In the “search” page, users can search all entries in three ways: by ncRNAs, by drugs, or by cancers. In the “browse” page, users can browse by clicking “ncRNAs”, “drugs”, or “cancer type” according to their purpose, the information would be listed as leaf nodes. In addition, the NoncoRNA also provides “quick search” function in the home page and search interface, such as miR-200, glioma, and temozolomide. Through clicking “more”, you can obtain detailed information. Figure 1 shows the more details, the entry contains detailed information on the ncRNAs, drugs, and cancers, the ncRNA expression pattern and experimental detection techniques, drug response, target gene, pathways, literature references, and other information. In addition, all data in the database can be obtained by the function of download. The NoncoRNA provides two formats of the downloadable file in TXT and Excel formats, respectively. The submit function enables communication between users and websites. Users enable to submit novel experimentally supported ncRNA-drug-cancer association. The help function can teach users how to use NoncoRNA. In addition, the web proved some query examples, it also helps users better understand how to use NoncoRNA.
In conclusion, NoncoRNA may serve as an immeasurable source for drug resistance research in human cancer. Compared with other databases, the NoncoRNA includes 3 distinctive features: (i) first providing the relationship between circRNAs, piRNAs, and drug resistance in cancers; (ii) 3294 lncRNAs were provided from our laboratory database by microarray analysis, which has not been studied in the field of gliomas; (iii) exhibiting some relationship between ncRNAs and drug resistance in cancer. Meanwhile, we will update and improve the database every 2 months. So we can use this relationship to develop the function of ncRNA in different cancers and drugs, and even to predict the new function in other cancers and drugs. Anyway, NoncoRNA provides a reliable database platform for a wide range of scientific researchers.
Supplementary information
Additional file 1: Table S1. Summary of the top 5 ncRNAs with references for most common 10 drugs. Table S2. Summary of cancers associated with ncRNAs.
Acknowledgements
We thank the members of the Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Neuroscience Institute for their fruitful discussions and technical assistance.
Abbreviations
- circRNA
Circular RNA
- lncRNA
Long non-coding RNA
- miRNA
MicroRNA
- ncRNA
Non-coding RNA
- piRNA
PIWI-interacting RNA
- qRT-PCR
Quantitative real time polymerase chain reaction
Authors’ contributions
JC, ZZ, and CJ designed the study. LL, WP, WZ, MX, ZC, LZ, QT, ZY, HB, and LS collected, analyzed, and interpreted the data. ZZ built the website. LL and WP wrote and edited the manuscript, and all authors read and approved the manuscript.
Funding
National Natural Science Foundation of China [no. 81702972, no. 81874204, no. 81772666, no. 81972817]; China Postdoctoral Science Foundation [2018 M640305]; The Research Project of the Chinese Society of Neuro-oncology, CACA [CSNO-2016-MSD12]; Heilongjiang Postdoctoral Science Foundation [LBH-Z18103]; The Research Project of the Health and Family Planning Commission of Heilongjiang Province [2017-201].
Availability of data and materials
All data obtained and/or analyzed in this study were available from the NoncoRNA (http://www.ncdtcdb.cn:8080/NoncoRNA/).
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Lulu Li and Pengfei Wu contributed equally to this work.
Contributor Information
Chuanlu Jiang, Email: jcl6688@163.com.
Zheng Zhao, Email: zhaozheng0503@sina.com.
Jinquan Cai, Email: caijinquan666777@126.com.
Supplementary information
Supplementary information accompanies this paper at 10.1186/s13045-020-00849-7.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Additional file 1: Table S1. Summary of the top 5 ncRNAs with references for most common 10 drugs. Table S2. Summary of cancers associated with ncRNAs.
Data Availability Statement
All data obtained and/or analyzed in this study were available from the NoncoRNA (http://www.ncdtcdb.cn:8080/NoncoRNA/).