Dataset Information

Reconstruction and analysis of the aberrant lncRNA-miRNA-mRNA network based on competitive endogenous RNA in adenoid cystic carcinoma of the salivary gland

ABSTRACT:

Background

The aim of this work was to investigate the competing endogenous RNA (ceRNA) network in adenoid cystic carcinoma of the salivary gland (SACC).

Methods

Differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) between cancer tissues and normal salivary gland (NSG) in ACC were identified using data from the Gene Expression Omnibus (GEO) database. Functional annotation and pathway enrichment analysis of DEmRNAs were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The miRNAs that are targeted by lncRNAs were predicted using miRanda and PITA, while the target mRNAs of miRNAs were retrieved from miRanda, miRWalk, and TargetScan. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and then we constructed the lncRNA-miRNA-mRNA networks of ACC.

Results

Differentially expressed RNAs were identified in SACC. Upon comparing cancer tissues and NSG tissues, 103 upregulated and 52 downregulated lncRNAs and 745 upregulated and 866 downregulated mRNAs were identified in GSE88804; in addition, 39 upregulated and 43 downregulated miRNAs were identified in GSE117275. GO enrichment analyses revealed that the most relevant GO terms were regulation of transcription DNA-templated, transcription DNA-templated, and cell division. KEGG pathway enrichment analysis showed that differentially expressed genes (DEGs) were mainly enriched in the cell cycle, pathways in cancer, PI3K-Akt signaling pathway, breast cancer, and microRNAs in cancer. The PPI network consisted of 27 upregulated and 54 downregulated mRNAs. By constructing ceRNA network, NONHSAT251752.1-hsa-miR-6817-5p-NOTCH1, NONHSAT251752.1-hsa-miR-204-5p/hsa-miR-138-5p-CDK6 regulatory axises were identified and all genes in the network were verified by qRT-PCR.

Conclusions

The present study constructed ceRNA networks in SACC and provided a novel perspective of the molecular mechanisms for SACC.

SUBMITTER: Tang Y

PROVIDER: S-EPMC8798187 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Adenoid cystic carcinoma (ACC) is a slow growing, but relentless cancer. Due to its rarity and lack of understanding of its molecular etiology, no standard chemotherapy for ACC currently exists and many patients suffer from recurrent and/or metastatic disease. As such, development of safe and effective therapies is imperative. To describe and summarize existing clinical trial studies and preclinical discoveries, we surveyed the PubMed on developmental therapeutics for ACC. Objective response rates to monotherapy with cytotoxic agents were approximately 10% with cisplatin, 5-FU, gemcitabine, mitoxantrone, epirubicin, vinorelbine and paclitaxel. The most studied combination therapies were cyclophosphamide-doxorubicin-cisplatin (CAP) and cisplatin-vinorelbine, with an objective response rate of 18-31%. Among molecularly targeted drugs, the most studied drugs are inhibitors targeting the vascular endothelial growth factor receptor (VEGFR) to inhibit tumor angiogenesis. Among those, lenvatinib and axitinib showed a relatively high objective response rate of 11-16% and 9-17%, respectively. Given high recurrence rates and chemoresistance of ACC, treatments targeting cancer stem cells (CSC), which function as tumor-initiating cells and drive chemoresistance, may be particularly valuable. CSC have been shown to be targetable via MYB, Notch1, p53 and epigenetic mechanisms. Myb overexpression is characteristic in ACC but was previously thought to present a difficult target due to its nature as a transcription factor. However, due to the development Myb-targeted inhibitors and an ongoing clinical trial of MYB-targeted cancer vaccine therapy, MYB is becoming an increasingly attractive therapeutic target. Drugs targeting NOTCH signaling demonstrated 5-17% response rate in phase I clinical trials. Within the field of epigenetics, treatment with PRMT5 inhibitors has shown 21% partial response rate in phase I clinical trial. Immunotherapies, such as PD-1 inhibitors, are also associated with CSC, but have not been effective against ACC. However, clinical trials of cancer vaccine therapies are actively being conducted. In addition to conventional chemotherapies and inhibitors of angiogenesis, the emergence of new therapies such as immunotherapy and those targeting cancer stemness is expected to bring clinical benefits to patients in the future.