Peer Review #2 of "miR-875-5p exerts tumor-promoting function via down-regulation of CAPZA1 in esophageal squamous cell carcinoma (v0.1)" [peer_review]

X Zhang
2021 unpublished
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer deaths worldwide. Currently, efficient genetic markers for diagnosis and treatment of ESCC are lacking. MicroRNAs (miRNAs) are global genetic regulators that control cancer gene expression by binding to the 3'untranslated regions (3'UTRs) of targeting mRNAs. In addition, miRNAs function as oncogenes or tumor suppressors in the progression of tumors. In the current study, we found that hsa-miR-875-5p (miR-875-5p)
more » ... ibited amplification in ESCC according to the TCGA database. Then, xCELLigence Real-Time Cell Analyzer (RTCA)-MP system and colony formation assays were employed to detect cell proliferationand colony formationability. The results showed that miR-875-5p promoted the proliferation ESCC cells. Subsequently,transwell results indicated that miR-875-5p promoted the invasion and migration of ESCC cells. Furthermore, we showed that miR-875-5p was able to bind to CAPZA13'UTR, which contains the single nucleotide polymorphism (SNP), rs373245753, as reported in our previous study involving WGS and WES on ESCC. Subsequently, mRNA affinity pull-down assays verifiedthat the SNP disrupts miR-875-5p binding to CAPZA1. The current study is the first demonstration that miR-875-5p may function as an oncogene via down-regulation of CAPZA1expression in ESCC. PeerJ reviewing PDF | (Manuscript to be reviewed 1 2 miR-875-5p exerts tumor-promoting function via down-regulation of CAPZA1 in 3 esophageal squamous cell carcinoma 4 5 Abstract 21 22 Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer deaths 23 worldwide. Currently, efficient genetic markers for diagnosis and treatment of ESCC are lacking. 24 MicroRNAs (miRNAs) are global genetic regulators that control cancer gene expression by 25 binding to the 3'untranslated regions (3'UTRs) of targeting mRNAs. In addition, miRNAs 26 function as oncogenes or tumor suppressors in the progression of tumors. In the current study, 27 we found that hsa-miR-875-5p (miR-875-5p) exhibited amplification in ESCC according to the 28 TCGA database. Then, xCELLigence Real-Time Cell Analyzer (RTCA)-MP system and colony 29 formation assays were employed to detect cell proliferation and colony formation ability. The 30 results showed that miR-875-5p promoted the proliferation of ESCC cells. Subsequently, 31 transwell results indicated that miR-875-5p promoted the invasion and migration of ESCC cells. 32 Furthermore, we showed that miR-875-5p was able to bind to CAPZA1 3'UTR, which contains 33 the single nucleotide polymorphism (SNP), rs373245753, as reported in our previous study PeerJ reviewing PDF | (Manuscript to be reviewed 34 involving WGS and WES on ESCC. Subsequently, mRNA affinity pull-down assays verified 35 that the SNP disrupts miR-875-5p binding to CAPZA1. The current study is the first 36 demonstration that miR-875-5p may function as an oncogene via down-regulation of CAPZA1 37 expression in ESCC. 38 39 Introduction 40 41 Esophageal cancer is one of the most aggressive cancers worldwide and is categorized into 42 two subtypes: esophageal adenocarcinoma (EAC); and esophageal squamous cell carcinoma 43 (ESCC) (Pennathur et al. 2013). Approximately 70% of the worldwide cases of ESCC occur in 44 China, which is characterized by late detection and widespread metastases (Lin et al. 2010; 45 Pennathur et al. 2013). Like other common cancers, ESCC is a complex trait caused by genetic 46 and environmental factors (Engel et al. 1991; Pennathur et al. 2013). 47 MicroRNAs (miRNAs) are a class of RNA molecules, approximately 22nt in length, that 48 regulate gene expression through base pairing with the 3'UTRs of target mRNAs, resulting in 49 mRNA cleavage or translation repression (Bartel. 2014 ; Lee & Vasudevan. 2013). Recent 50 studies have shown that miRNAs are aberrantly expressed in many human cancers and function 51 as oncogenes or tumor suppressors in the initiation, development, and metastasis of human 52 carcinomas (Chen. 2005; Esquela-Kerscher & Slack. 2006 ; Nohata et al. 2013). It has been 53 reported that Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in 54 colorectal cancer (Han et al. 2012). Furthermore, miRNA-424 may function as a tumor 55 suppressor in endometrial carcinoma cells by targeting E2F7 (Quan et al. 2015). It has also been 56 reported that miR-223-3p has a tumor-promoting role in head and neck squamous cell carcinoma 57 (Bozec et al. 2017). Indeed, miR-875-5p is amplified 6% and 5% in EAC and ESCC from the 58 TCGA database, respectively. There are several studies that have reported that miR-875-5p has 59 an important role in tumor progression. Specifically, miR-875-5p promotes the invasion of lung 60 cancer cells by inhibiting SATB2 (Wang et al. 2017). Up-regulation of miR-875-5p induces 61 poorly differentiated thyroid carcinoma (PDTC) cell proliferation and reduces apoptosis and 62 radioiodine uptake in vitro by down-regulating NIS (Tang et al. 2019), however, a limited 63 number of studies have focused on the function of miR-875-5p in ESCC. We conducted a series 64 of functional assays to assess the effects of miR-875-5p on ESCC cell lines. 65 It has been reported that approximately 30% of human genes are regulated by miRNAs 66 (Carthew. 2006). We used TargetScan (Lewis et al. 2003) and miRanda (John et al. 2005) PeerJ reviewing PDF | (
doi:10.7287/peerj.10020v0.1/reviews/2 fatcat:yddro4glzvdqldrlpr3f37e5va