Abstract
BackgroundCervical cancer (CC) endangers women’s health in the world range. Accumulating studies have revealed the crucial regulatory role of long non-coding RNAs (lncRNAs) in multiple malignancies, including CC. Our study aimed to explore the role of lncRNA double homeobox A pseudogene 8 (DUXAP8) in cervical carcinogenesis.MethodsGene expressions in CC were assessed by RT-qPCR. Function experiments and tube formation assays were performed to evaluate the role of DUXAP8 in CC cells. Subcellular fractionation and FISH assays were conducted to determine the subcellular location of DUXAP8. Luciferase reporter, RNA pull down and RIP assays were conducted to investigate the mechanism of DUXAP8.ResultsDUXAP8 was notably upregulated in CC cells. Downregulation of DUXAP8 repressed cell malignant behaviors and angiogenesis in CC. Mechanically, DUXAP8 boosted the expression of reticulocalbin-2 (RCN2) through relieving the binding of miR-1297 to RCN2 3’-UTR. Moreover, miR-1297 inhibition and RCN2 overexpression could counteract the inhibitory effects of DUXAP8 knockdown on the malignant phenotypes of CC cells. Besides, enhanced RCN2 expression restored the tumor growth in vivo that was inhibited by DUXAP8 repression.ConclusionsDUXAP8 promotes malignant behaviors in CC cells via regulating miR-1297/RCN2 axis.Graphical
Highlights
Cervical cancer (CC) endangers women’s health in the world range
double homeobox A pseudogene 8 (DUXAP8) is aberrantly highly expressed in CC and silencing DUXAP8 suppresses the malignant behaviors of CC cells Realtime quantitative PCR (RT-qPCR) analysis was performed in CC cell lines and normal cervical epithelial cell line Ect1/E6E7 to explore the expression level of DUXAP8
Results manifested that DUXAP8 expression was markedly increased in CC cell lines, especially in caSki and HeLa cells (Fig. 1A), which suggested that DUXAP8 might be implicated in the progression of CC
Summary
Cervical cancer (CC) endangers women’s health in the world range. Accumulating studies have revealed the crucial regulatory role of long non-coding RNAs (lncRNAs) in multiple malignancies, including CC. Our study aimed to explore the role of lncRNA double homeobox A pseudogene 8 (DUXAP8) in cervical carcinogenesis. A great number of lncRNAs have been reported to play pivotal roles in a series of cellular biological processes, such as cell proliferation, differentiation, apoptosis, migration and epithelial mesenchymal transition (EMT) [8, 9]. DUXAP8 knockdown suppresses cell proliferation and facilitates cell apoptosis in pancreatic cancer [10]. LncRNAs have been discovered to function as a class of competing endogenous RNAs (ceRNAs) to posttranscriptionally regulate gene expressions. DUXAP8 serves as ceRNA for miR-577 to facilitate the invasion and migration of colorectal cancer cells via regulating RAB14 [13].
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