HOTAIR Contributes to Stemness Acquisition of Cervical Cancer through Regulating miR-203 Interaction with ZEB1 on Epithelial-Mesenchymal Transition

Abstract

Cervical cancer stem cells contribute respond to considerable recurrence and metastasis of patients with cervical cancer. The stemness properties were partly regulated by the interaction of lncRNAs and miRNAs. HOTAIR functions as an oncogenic lncRNA. Previous research studies revealed its role in regulating stemness properties in various cancers. However, the role of HOTAIR in cervical cancer stem cells is still unknown. Here, cisplatin-resistant and serum-free cultured cells exhibited stem cells properties. Cervical cancer stem cells exhibited greater invasion and migration compared with their parental cells, which was similar to cells overexpressing HOTAIR. HOTAIR was significantly overexpressed in cervical cancer stem cells, and knockdown of HOTAIR generated statistical downregulation of stemness markers. Additionally, HOTAIR expression was negatively correlated with the level of miR-203, which was found to be an inhibitory miRNA in regulating the expressions of stemness markers. Also, miR-203 expression was negatively correlated with ZEB1. These findings suggested that HOTAIR should be a positive contributor in stemness acquisition of cervical cancer cells, and this effect should correlate with the interaction with miR-203, which can be suppressed by ZEB1.

Aberrant Methylation of 20 miRNA Genes Specifically Involved in Various Steps of Ovarian Carcinoma Spread: From Primary Tumors to Peritoneal Macroscopic Metastases

“…Furthermore, the inhibitory effect of miR-203a-3p on these target genes is supported by the significant negative correlation between the expression levels of miR-203a-3p and mRNA of ZEB1 and ZEB2. The effect of miR-203 (the commonly used name of miR-203a-3p) on ZEB1 and ZEB2 genes was previously shown in many cancer types, such as lung, gastric, cervical, prostate, colon, and renal cancers, as well as glioblastoma, cholangiocarcinoma, and nasopharyngeal carcinoma, for both ZEB1 [24][25][26][27][28] and ZEB2 [29][30][31][32][33][34]. However, the inhibitory effect of miR-203a-3p/miR-203 on the expression level of ZEB1 and ZEB2 in OvCa was not previously reported in the literature (PubMed on 15 November 2021).…”

Pharmacological inhibition of HDAC6 overcomes cisplatin chemoresistance by targeting cancer stem cells in oral squamous cell carcinoma

“…As expected, the administration of cisplatin increases the stemness of the CSCÀ subpopulation, probably activating a dedifferentiation program that increases CSC accumulation. 11 However, the administration of tubastatin A promoted a significant reduction of stemness in the CSC+ from both cell lines and, when combined with cisplatin, tubastatin A could reverse the effect of cisplatin on stem cells accumulation (Figure 5A,B).…”

Association between long non‑coding RNA HOTAIR polymorphism and lung cancer risk: A systematic review and meta‑analysis

“…Apart from the p21 WAF1 /CIP1 and HOXA5 pathways, the most commonly acknowledged mechanism of HOTAIR is through the axis of microRNA (miR) and downstream signaling molecules. These axes include but are not limited to the following: HOTAIR/miR-222-3p/Cyclin Dependent Kinase 19 axis ( 46 ), HOTAIR/specificity protein 1/miR-199a axis ( 47 ), HOTAIR/miR-29b/phosphate and tension homology deleted on chromosome 10/PI3K axis ( 48 ), HOTAIR/miR-203/zinc finger E-box binding homeobox 1 axis ( 49 ), HOTAIR/estrogen receptor 1/miR-130b-3p axis ( 50 ), HOTAIR/miR-34a/Janus kinase 2/STAT3 axis ( 51 ), HOTAIR/miR-129-5p/ribosomal protein L14 axis ( 52 ), HOTAIR/miR-129-5p/frizzled class receptor 7 axis ( 53 ) and HOTAIR/miR-149-5p/doublecortin-like kinase 1 axis ( 54 ). Furthermore, HOTAIR also interacts with several classic signaling pathways, which are commonly involved in oncogenesis, such as CCL22 signaling ( 55 ), the Wnt/β-catenin signaling pathway ( 56 ), EZH2 and H3K27 methylation signaling ( 57 ).…”