MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway

Abstract

BackgroundWe are committed to investigate miR-218-5 effects on the progression of cervical cancer (CC) cell and find out the molecular mechanism.MethodsGSE9750 was obtained from GEO database and R Limma package was applied to filter out dysregulated genes. The pathways were enriched by GSEA software, ClusterProfiler and enrichplot packages to predict the function of DEGs. The binding sites of LYN were detected by miRanda and TargetScan. The miR2Disease database was used to find miRNAs related with CC. The expression of miR-218-5p and LYN were quantified by qRT-PCR and that of LYN protein was measured by western blot. The targeted relationships between miR-218-5p and LYN were verified by dual-luciferase reporter assay. Colony formation assays, wound healing, transwell invasion assay and flow cytometer analysis were performed to investigate the roles that miR-218-5p and LYN played in migration, invasion and death of cervical carcinoma. Xenografts established in nude mice were used to assess tumor growth in vivo.ResultsThe highly expressed mRNA LYN was selected by microarray analysis in GSE9750. NF-κB signaling pathway was enriched base on GSEA results. The expression of miR-218-5p was lower but LYN was higher in CC primary tumors compared with normal control. In addition, miR-218-5p could regulate the expression of LYN in HeLa cells negatively. Overexpression of LYN could promote cell migration and invasion, but inhibit cell death in vitro, and also promote tumor formation in vivo via activating NF-κB signaling pathway which could be reversed by miR-218-5p.ConclusionsMiR-218-5p suppressed the progression of CC via LYN/NF-κB signaling pathway.

MicroRNA Involvement in Signaling Pathways During Viral Infection

“…Even though E1, E2, L1 and L2 are always encountered in all HPVs, the other genes may vary (Stubenrauch et al, 2007;Nobre et al, 2009). The major oncogenes are considered to be E5, E6 and E7, which are also known for altering a variety of signaling pathways, such as Wnt, Notch, PI3K/Akt, MAPK, IFN and NF-κB and others (Gupta et al, 2018;Xu et al, 2018;Wang and Chen, 2019). However, studies have demonstrated that the HPV infection could alter the interaction between miRNAs and some of these pathways.…”

“…In the case of oral cancers caused by HPV16, the excessive expression of E6 and E7 oncogenes and the interaction with the NF-κB pathway lead to a better tumor differentiation, as well as an improved prognosis (Gupta et al, 2018). There were two miRNAs found to interact with this signaling pathway during HPV infection, and more specifically, in cervical cancers: miR-143-3p and miR-218-5p (Xu et al, 2018). Both of them have the mRNA LYN as a target, which was found to be highly expressed in HPV induced cervical cancers, thus increasing the activity of NF-κB pathway.…”

ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis

“…Recently, miRNAs have been shown to be deregulated in pancreatic cancer, affecting several steps of initiation and aggressiveness of the disease by directly regulating target genes expression [25]. Among these miRNAs, miR-218-5p was found to play pivotal roles in many malignant tumors [26][27][28]. For example, miR-218-5p upregulation repressed gastric cancer growth and metastasis by directly regulating CDK6/CyclinD1 [28].…”

<p>Long Non-Coding RNA HULC Promotes Cervical Cancer Cell Proliferation, Migration and Invasion via miR-218/TPD52 Axis</p>

“…22 Subsequent research provided evidence that abundant miR-218 increased the radiosensitivity in cervical cancer cells. 23 More recently, Zhu et al 12,13 reported that miR-218 also produced anti-tumor effects on cervical cancer cells in vitro. In line with this, our results showed that miR-218 mimics significantly inhibited cervical cancer cell proliferation, migration and invasion.…”

“…MiR-218 was downregulated in cervical cancer, and miR-218 overexpression was found to inhibit cervical cancer cell viability, cell growth and metastasis, and promote apoptosis. 12,13 Bioinformatics using miRanda predicted that HULC and miR-218 have partially complementary sequences, suggesting that HULC may function as a "miRNA sponge" of miR-218. The prediction of target genes using TargetScan showed that there were binding sites between miR-218 and 3ʹ-UTR of the oncogenic tumor protein D52 (TPD52) mRNA.…”