Long noncoding RNA KCNQ1OT1 promotes proliferation, migration, and invasion in maxillary sinus squamous cell carcinoma by regulating miR‐204/EphA7 axis

Abstract

Long noncoding RNAs have been demonstrated to contribute to the development and progression of various cancers. However, the underlying regulatory mechanisms of KCNQ1OT1 in tumorigenesis of maxillary sinus squamous cell carcinoma (MSSCC) remain unknown. Herein, we found that KCNQ1OT1 expression was markedly upregulated in MSSCC tissues and MSSCC cell line (IMC‐3) by using quantitative reverse transcription‐polymerase chain reaction. Loss‐of‐function experiments revealed that the deletion of KCNQ1OT1 inhibited cell proliferation, migration, and invasion. Moreover, we confirmed KCNQ1OT1 could directly interact with miR‐204 by bioinformatic prediction and dual luciferase assay, and miR‐204 inhibitor markedly reversed MSSCC tumor phenotypes induced by shKCNQ1OT1. Finally, we demonstrated that KCNQ1OT1/miR‐204 facilitated MSSCC progression by regulating Eph receptor A7 (EphA7). Taken together, these results revealed a novel regulatory mechanism KCNQ1OT1/miR‐204/EphA7 axis, which could provide a new understanding of MSSCC tumorigenesis and develop potential targets for MSSCC therapy.

KCNQ1OT1: An Oncogenic Long Noncoding RNA

“…In a xenograft mouse model, knockdown of KCNQ1OT1 inhibited CRC cell growth and decreased tumor volume, while overexpression of KCNQ1OT1 induced protective autophagy and chemoresistance to oxaliplatin (OXA) by sponging miR-34a and upregulating autophagy-related 4B (Atg4B) [ 2 ]. Sun et al, showed that KCNQ1OT1 acted as a sponge of miR-204 in the progression of MSSCC and explored the role of ceRNA regulation of the KCNQ1OT1/miR-204/EphA7 axis [ 17 ]. Cell-based studies indicate that KCNQ1OT1 knockdown inhibited cell proliferation and promoted apoptosis and cell differentiation in HL-60 and U937 AML cells by acting as a ceRNA for miR-326 and targeting c-Myc (Myc proto-oncogene, basic helix-loop-helix (bHLH) transcription factor) [ 18 ].…”

“…LncRNAs can control protein-coding and noncoding gene expression and function in tissue and developmental-stage specific manner by several mechanisms, including regulation of chromatin remodeling, RNA splicing events, transcriptional activation/repression, mRNA stability and translation by homologous base pairing, and post-transcriptional regulation of protein activity [ 11 , 13 , 14 , 15 , 16 ]. LncRNAs can interact with a variety of partners such as RNA/DNA-binding proteins, transcription factors, chromatin-modifying complexes, RNA transcripts, mature mRNA, microRNA (miRNA), DNA, and chromatin [ 17 ]. Moreover, lncRNAs harboring microRNA recognition elements also function as competing endogenous RNAs (ceRNAs) that bind to and “sponge” miRNAs, downregulating and preventing them from binding to and regulating their target mRNAs [ 12 , 18 , 19 ].…”

The role of altered microRNA expression in premalignant and malignant head and neck lesions with epithelial origin

“…One of the other miRs that are known as tumor suppressor factor are miR‐122 that has a critical role in inhibiting the tumorigenesis and angiogenesis in OLP and let‐7d that preventthe tumorigenesis process and downregulated in head and neck squamous cell carcinoma (HNSCC) (Tables 3,4). 35,39 Also miR‐204 sole as tumor suppressor that involved in pathogenesis of relative common carcinoma of the maxillary sinus by targeting EphA7 gene 55 . The dual regulatory role of miRNAs generalizes to different tissues and provides complication in a selection of specific microRNA for therapeutic strategies.…”

“…35,39 Also miR-204 sole as tumor suppressor that involved in pathogenesis of relative common carcinoma of the maxillary sinus by targeting EphA7 gene. 55 The dual regulatory role of miRNAs generalizes to different tissues and provides complication in a selection of specific microRNA for therapeutic strategies. It seems induce the expression of miRNA with tumor suppressor function or decrease the expression of miRNA with an oncogenic role can help us to use them as valuable therapeutic biomarkers.…”

The role of long non-coding RNAs in the pathogenesis of head and neck squamous cell carcinoma

“…For example, LncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) has been shown to facilitate the proliferation of maxillary sinus squamous cell carcinoma cells through inhibiting miR-204 expression and restoring EphA7 expression. 51 It can also sponge miR185-5p to promote the migration and proliferation of OSCC cells. 65 Besides, KCNQ1OT1 contributes to the cisplatin resistance of TSCC through the miR-124-3p/TRIM14 axis.…”