Long non-coding RNA HOTAIR regulates proliferation, migration and invasion of human cervical cancer cells by modulating expression of MAPK1

Abstract

Introduction: Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are dysregulated in cancer cells and may be responsible for the development and progression of this disease. Herein, the role and therapeutic potential of aberrantly expressed lncRNA HOTAIR were investigated in cervical cancer. Material and methods: The expression profile of the lncRNA HOTAIR was determined by quantitative RT-PCR. CCK-8 and colony formation assays were used for determination of cell viability. DAPI and annexin V/PI assays were used for detection of apoptosis. Wound healing and transwell assays were used to monitor cell migration and invasion. Results: The results showed that the expression of lncRNA HOTAIR was significantly (p < 0.01) upregulated (up to 4.1-fold) in cervical cancer cell lines. Silencing of lncRNA HOTAIR expression resulted in inhibition of the proliferation of the DoTc2 cervical cancer cells via induction of apoptotic cell death. HOTAIR silencing also resulted in decrease of the migration and the invasive properties of the cervical cancer cells. HOTAIR has been reported to interact with MAPK1 in cancer cells, and in this study MAPK1 was found to be overexpressed (up to 3.7-fold) in all the cervical cancer cells and silencing of HOTAIR inhibited the expression of MAPK1 in DoTc2 cervical cancer cells. Silencing of MAPK1 in DoTc2 cells also inhibited their proliferation and metastasis via induction of apoptosis. Co-transfection experiments showed that silencing of MAPK1 and lncRNA HOTAIR causes inhibition of DoTc2 cell growth synergistically. Conclusions: These results indicate that lncRNA HOTAIR may prove to be an important therapeutic target for management of cervical cancer.

LncRNA HOTAIR Promotes Chemoresistance by Facilitating Epithelial to Mesenchymal Transition through miR-29b/PTEN/PI3K Signaling in Cervical Cancer

“…Therefore, the effects of HOTAIR and miR-29b on the malignant phenotypes of human cervical cancer cells were determined in vitro, and the potential interaction of HOTAIR with miR-29b in cervical cancer cells was explored in this study. The data showed that, consistent with previous studies, HOTAIR could promote proliferation and migration, while miR-29b suppressed cervical cancer cell malignancy in vitro [Zhang et al, 2019;Liu et al, 2020]. In addition, the negative correlation between HOTAIR and miR-29b in cervical cancer cells, as well as significant reduction in luciferase activity of pmirGLO-HOTAIR-Wt due to miR-29b mimics, indicated that aberrantly expressed HOTAIR could competitively bind to miR-29b thus suppressing the positive effect of miR-29b on the progression of cervical cancer.…”

Circulating exosomal lncRNAs in patients with chronic coronary syndromes

“…LncRNAs are noncoding RNAs longer than 200 nucleotides, which regulate gene expression at the transcriptional, post-transcriptional, and translational levels. Previous studies have proved that lncRNAs were involved in regulating pathophysiological conditions, such as cancer [22][23][24], autoimmune diseases [25], and others [26]. In CAD, lncRNAs were found to be differently expressed in atherosclerotic coronary artery plaques [27], and were proved to serve as biomarkers to diagnose CAD [11][12][13][14].…”

Long noncoding RNA HOTAIR as a biomarker for the detection of Cervical Cancer and Cervical Intraepithelial Neoplasia

“…But no association was observed with histological types [18]. HOTAIR promoted cell proliferation, migration, and invasion in cervical cancer cell lines through different mechanisms including complex interactions with micro-RNAs and proteins of cancer related signaling pathways such as NOTCH and mitogen-activated protein kinase (MAPK) [15,17,31]. Moreover, HOTAIR regulated the expression of genes related to cell motility and metastasis such as vascular endothelial growth factor, matrix metalloproteinase-9 and (EMT)-related genes [30].…”

“…Because of the limitations of cytology and HPV testing alone in cervical cancer screening, other alternatives are currently investigated, especially noncoding RNAs. For instance, a study found that 12 miRNAs may distinguish high-grade CIN from normal tissues of the cervix [31]. Another study found a six-microRNA signature that was able to discriminate low grade CINs with a sensitivity range between 83 and 95%, and specificity from 83 to 97% (AUC ranging from 0.91 to 0.99), as well as discriminating high grade CINs with a sensitivity ranging from 80 to 92%, and specificity ranging from 81 to 93% (AUC ranging from 0.88 to 0.98) [32].…”