LncRNA HOTAIR regulates the expression of E-cadherin to affect nasopharyngeal carcinoma progression by recruiting histone methylase EZH2 to mediate H3K27 trimethylation

Abstract

Background In recent years, there has been increasing evidence for the function of long non-coding RNA (lncRNA) in nasopharyngeal carcinoma (NPC).. We aim to delve into the position of lncRNA HOTAIR, together with EZH2, E-cadherin and H3K27me3 in NPC and explore the related mechanisms. Methods RT-qPCR and western blot analysis were carried out for detecting lncRNA HOTAIR, EZH2, E-cadherin and H3K27me3 expression in NPC tissues and cells. Moreover, the correlations between lncRNA HOTAIR and EZH2 expression and the clinicopathological characteristics and prognosis of patients with NPC were observed. NPC cell biological functions were examined through gain-of and loss-of function assays. RIP and ChIP assays were applied to detect whether lncRNA HOTAIR in NPC cells could regulate E-cadherin by recruiting EZH2 to mediate trimethylation of H3K27. Results LncRNA HOTAIR, EZH2, and H3K27me3 were richly expressed in NPC tissues and cells, and E-cadherin was lowly expressed. The prognosis of patients with overexpression of lncRNA HOTAIR and EZH2 was worse than that of patients with theirs low expression. Down-regulation of either HOTAIR or EZH2 inhibited cell proliferation, promoted apoptosis, suppressed migration and invasion and inhibited tumor growth. HOTAIR recruited histone methylase EZH2 to mediate trimethylation of H3K27 and regulated E-cadherin expression. Conclusion Our study suggests that lncRNA HOTAIR inhibits the expression of E-cadherin by stimulating the trimethylation of H3K27 by histone methylase EZH2 to promote cell migration, proliferation, and inhibit apoptosis of NPC cells.

KTN1-AS1, a SOX2-mediated lncRNA, activates EMT process through RBBP4/HDAC1/E-cadherin axis in esophageal squamous cell carcinoma

“…E-cadherin, a typical epithelial cell marker, is a Ca 2+ dependent transmembrane glycoprotein closely related to intercellular adhesion. The dysregulation of E-cadherin expression that leads to carcinogenesis happens mostly at the epigenetic level (33,34). HDACs are enzymes mediating the removal of acetyl from lysine residues in either histones or other proteins, causing the repression of gene transcription and subsequent changes in signaling events (35), and HDAC1 was demonstrated to be involved in the transcriptional regulation of Ecadherin expression (17,18).…”

Clinicopathological and prognostic significance of the long non-coding RNA HOTAIR high expression in head and neck squamous cell carcinoma: a systematic review and meta-analysis

“…After reading the full text, 18 studies were identified as eligible articles. According to the inclusion and exclusion criteria, 9 pieces of literature were eventually included in this study (26,(36)(37)(38)(42)(43)(44)(45)(46). All of the included studies were published between 2012 and 2021 with sample sizes between 44 and 425 patients and a total of 1,043 patients.…”

“…All of the included studies were published between 2012 and 2021 with sample sizes between 44 and 425 patients and a total of 1,043 patients. Seven studies with a total of 546 patients provided an association between the clinicopathological characteristics of HNSCC patients and HOTAIR expressions (26,(36)(37)(38)(43)(44)(45), and 6 studies with a total of 856 patients provided the correlation between HOTAIR expressions and HNSCC prognoses (26,36,38,42,45,46). Among the 9 studies, 7 studies were conducted in China, 1 in India (37), and 1 study involving survival outcomes was derived from the TCGA database (46).…”

“…Next, HOTAIR expression was compared among patients with HNSCC with different Lymphnode metastasis statuses from 7 studies that included in 541 patients (26,(36)(37)(38)(43)(44)(45). Among the patients with lymphnode metastasis (N1-N3), 196 patients exhibited high expressions for HOTAIR and 141 patients exhibited low expressions.…”

“…In total, 468 patients across 6 studies were assessed to determine the relationships between TNM stages and HOTAIR expressions (26,37,38,(43)(44)(45). Among the patients with high TNM stages (III-IV), 171 exhibited high HOTAIR expressions, and 121 exhibited low HOTAIR expressions.…”