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

Wenying Zhang,Jing Liu,Chengbin Ma,Qiongwei Wu,Yu Liu,Prasanna Kumar Santhekadur

doi:10.1155/2021/4190764

Wenying Zhang, Jing Liu + Show 4 more

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https://doi.org/10.1155/2021/4190764

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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.

Highlights

Despite considerable advances in screening, diagnosis, prevention, and treatment, cervical cancer is still one of the leading causes of cancer-related death in women worldwide [1, 2]
Stem-like cells were enriched from two human cervical cancer cell lines, HeLa and SiHa, in presence of cisplatin and in a serum-free medium. en, enriched cisplatin-resistant cells and serum-free cultured cells were submitted to detect the expressions of stem cell markers, including NANOG, OCT4, CD44, ALDH1, CD133, and SOX2
We found that transfection with small interference RNA targeting HOX transcript antisense intergenic RNA (HOTAIR) resulted in a statistical increase of miR-203 compared with those normal control cells (Figure 6(a)), indicating that miR-203 was negatively correlated with HOTAIR in cervical cancer cells

Summary

Introduction

Despite considerable advances in screening, diagnosis, prevention, and treatment, cervical cancer is still one of the leading causes of cancer-related death in women worldwide [1, 2]. Burgeoning evidence indicated that current cancer treatments failed to eradicate a subset of cells within tumor known as cancer stem cells (CSCs); this failure allows CSCs to self-renew and provoke tumor relapse [3]. Various long noncoding RNAs (lncRNAs) have been recognized crucial players in regulating CSC properties and allowing them to self-renew and promote tumor growth [4, 5]. HOX transcript antisense intergenic RNA (HOTAIR) is transcribed from the antisense strand of the homeobox gene C cluster (HOXC) and recognized as an oncogenic lncRNA in various types of malignant tumors, including cervix cancer. HOTAIR can recruit the MLL1 methyltransferase and induce H3K4me, thereby relaxing chromatin and allowing binding of transcription machinery [6, 7]. Rough aforementioned approaches, HOTAIR exerts its crucial effects on proliferation, migration, and invasion in cervical cancer. HOTAIR overexpression is believed to be associated with the acquisition of stem cell properties, which resulted in an increased tumor growth and metastatic

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