Construction and analysis of miRNA-mRNA regulatory networks in the radioresistance of nasopharyngeal carcinoma
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ORIGINAL ARTICLE
Construction and analysis of miRNA‑mRNA regulatory networks in the radioresistance of nasopharyngeal carcinoma Houyu Zhao1 · Aoshuang Chang1 · Junjun Ling1,3 · Wei Zhou2 · Huiping Ye1 · Xianlu Zhuo1 Received: 30 January 2020 / Accepted: 24 October 2020 © King Abdulaziz City for Science and Technology 2020
Abstract Radiotherapy has been the major treatment strategy for nasopharyngeal carcinoma (NPC), while the occurrence of radioresistance may lead to cancer recurrence or progression. This study aimed to identify the key microRNAs (miRNAs) and their target genes in the development of NPC radioresistance. Public microarray data were searched and analyzed to screen the differentially expressed miRNAs (DEMs) and genes (DEGs) between radioresistant and radiosensitive NPC samples. MiRNA-mRNA networks were constructed. As a result, 5 DEMs and 195 DEGs were screened out. The DEGs were enriched in various signaling pathways, such as Cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and Toll-like receptor signaling pathway. Several hub genes, such as IGF2, OLA1, BBS10, MMP9, and BBS7 were identified. A regulatory miRNA-mRNA network containing 87 miRNA-mRNA pairs was constructed. Then, 14 key miRNA-mRNA pairs that contained the hub genes were further filtered out. In the networks, miR-203a-3p had the largest number of target genes. Afterwards, the candidate pairs (miR-203a-3p/BTK and miR-484/OLA1) have been verified by a qRT-PCR assay. In summary, we identified several miRNAs and hub genes via big data screening. A total of 87 miRNA-mRNA pairs (including 14 key pairs) were predicted to play a crucial role in the development of NPC radioresistance. These data provide a bioinformatics basis for further exploring the molecular mechanism of radiotherapy resistance in NPC. Future studies are needed to validate the results. Keywords Nasopharyngeal carcinoma · Radioresistance · MicroRNA · Microarray · qRT-PCR
Introduction Nasopharyngeal carcinoma (NPC) is a kind of malignant tumor originated from the nasopharynx, which is characterized by low differentiation squamous cell carcinoma. Although NPC is a rare malignancy in the world, it is endemic in Southeast Asia (Gioacchini et al. 2017). Given its high radiosensitivity, the primary and standard treatment for NPC is radiotherapy. Nevertheless, in the course of treatment, the emergence of radioresistance significantly reduced the efficacy of radiotherapy. Thus, the survival rate of a
* Xianlu Zhuo [email protected] 1
Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
2
Chongqing Cancer Hospital, Chongqing 400030, China
3
Southwest Hospital, Army Medical University, Chongqing 400037, China
proportion of NPC patients remains low after radiotherapy. Evidence indicated that the occurrence of radioresistance may result in local recurrence or distant metastasis within 1.5 years in NPC patients (Zhao et al. 2017). To date, there have been few clinical measures to overcome the resistance of radiotherapy in NPC pa
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