Vol.:(0123456789) 1 3 Molecular Biology Reports https://doi.org/10.1007/s11033-020-05494-4 REVIEW Role of microRNAs in epidermal growth factor receptor signaling pathway in cervical cancer Nima Hemmat 1,2  · Ahad Mokhtarzadeh 1  · Mohammad Aghazadeh 3,4  · Farhad Jadidi‑Niaragh 1,5  · Behzad Baradaran 1,5  · Hossein Bannazadeh Baghi 1,2,4 Received: 5 December 2019 / Accepted: 3 May 2020 © Springer Nature B.V. 2020 Abstract Cervical cancer is one of the most common disorders in females all around the world. Similar to other types of cancer, several signaling pathways are demonstrated to be involved in the progression of this cancer including ERK/MAPK, PI3K/ AKT, apoptotic signaling pathways, Wnt, and epidermal growth factor receptor (EGFR). Various microRNAs (miRNAs) and their target genes involved in cervical cancer have been extracted from the kinds of literature of Scopus, Pubmed and Google scholar databases. Regarding the targets, some of them were found to belong in EGFR signaling pathways. The regulation patterns of these miRNA are diferent in cervical cancer; however, their main aim is to trigger EGFR signaling to proceed with cancer. Moreover, several predicted miRNAs were found to have some interactions with the diferentially expressed genes of cervical cancer which are the members of the EGFR signaling pathway by using miRWalk 3.0 (https:// mirwalk.umm.uni-heidelberg.de/) and TargetScan 7.1 (https://www.targetscan.org/vert_71/). Also, the microarray data were obtained from the NCBI-Gene Expression Omnibus (GEO) datasets of cervical cancer. In the present review, we highlight the miRNAs involved in cervical cancer and the role of their targets in the EGFR signaling pathway. Furthermore, some predicted miRNAs were the candidate to target EGFR signaling pathway members diferentially expressed in cervical cancer samples compared to normal samples. Keywords MicroRNAs · Cervical cancer · Epidermal growth factor receptor · ErbB family kinase receptors Introduction Cervical cancer is one of the most prevalent cancers in women worldwide which causes a high mortality rate yearly [1]. Cytologically, the stages of this cancer are divided into two groups, low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL); these stages are also known as cervical intraepithe- lial neoplasia (CIN) 1 to CIN3 in histological aspect. Several factors are reported to take part in the initiation and progres- sion of cervical cancer, however, the most well-known one is human papillomavirus (HPV) infection [2]. HPVs are known as the foremost causative infectious agent of approximately 4.8% of all human cancers [3]. These viruses belong to the Papillomaviridae family and have a preference for the mucosal and epithelial surfaces of the human body. They are non-enveloped, small, with a 7.9 kilobase pairs (Kbp) double-stranded DNA. The HPV genome encodes 8 structural and functional proteins includ- ing L1, L2 (structural), E1, E2, E4, E5, E6, and E7 (func- tional) [4]. The oncogenicity of this virus has been attrib- uted to the expression of its oncoprotein (E5, E6, and E7) in the host cell [5, 6]. According to our knowledge about the HPV life cycle, E6 and E7 could be expressed not only through the primary infection but also during the integrated form of the virus and could maintain the cancerous state of infected-cells [7–9]. HPV E7 also functions like E6 through * Hossein Bannazadeh Baghi hbannazadeh@tbzmed.ac.ir; hb.zadeh@gmail.com 1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2 Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, 5166/15731 Tabriz, Iran 3 Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran 4 Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 5 Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran