LncRNA HOTAIR promotes cell migration and invasion by regulating MKL1 via inhibition miR206 expression in HeLa cells

Peng Zheng,Ze Yin,Ying Luo,Yao Xu,Ying Wu,Tong-Cun Zhang

doi:10.1186/s12964-018-0216-3

Abstract

BackgroundLong non-coding RNAs (lncRNAs) have emerged as a new and crucial layer of gene regulation in recent years and regulate various biological processes such as carcinogenesis and metastasis. LncRNA HOTAIR, an oncogenic lncRNA, is involved in human tumorigenesis and dysregulated in cervical cancer. Megakaryoblastic leukemia 1 (MKL1), as a transcription coactivity factor, involved in cancer metastasis and cell differentiation. However, the precise mechanism of biological roles of HOTAIR and MKL1 in cancer cells remain unclear.MethodsThe expression levels of HOTAIR and MKL1 were measured by quantitative PCR (qPCR), immunoblotting, in situ hybridization (ISH) and immunohistochemistry (IHC). Wound-healing and transwell assays were used to examine the invasive abilities of HeLa cells. Luciferase reporter assays and CHIP were used to determine how MKL1 regulates HOTAIR. Tissue microarray and immunohistochemical staining were used to assess the correlation between HOTAIR and MKL1 in Cervical cancer tissues in vivo.ResultIn this study, we have identified that MKL1 had a role in the induction of migration and invasion in cervical cancer cells. Moreover, the expression level of MKL1, as the targeting gene of miR206, was decreased after HOTAIR inhibition in HeLa cells. Agreement with it, Highly level of MKL1 correlation with HOTAIR is validated in cervical cancer tissues. Importantly, HOTAIR is observed to participate in the silencing of miR206 expression. Interestingly, HOTAIR inhibition could also accelerate the expression of MKL1 in cytoplasm. What is more, MKL1 can activate the transcription of HOTAIR through binding the CArG box in the promoter of HOTAIR.ConclusionThese elucidates that the phenotypic effects of migration and invasion observed after HOTAIR inhibition, at least in part, through the regulation of MKL1 via inhibition of miR206 expression in HeLa cells. These data indicate the existence of a positive feedback loop between HOTAIR and MKL1. Together, these findings suggest that MKL1 is an important player in the functions of HOTAIR in the migration and invasion of cancer cells.

Highlights

Long non-coding RNAs have emerged as a new and crucial layer of gene regulation in recent years and regulate various biological processes such as carcinogenesis and metastasis
These elucidates that the phenotypic effects of migration and invasion observed after HOTAIR inhibition, at least in part, through the regulation of Megakaryoblastic leukemia 1 (MKL1) via inhibition of miR206 expression in HeLa cells
These findings suggest that MKL1 is an important player in the functions of HOTAIR in the migration and invasion of cancer cells

Summary

Introduction

Long non-coding RNAs (lncRNAs) have emerged as a new and crucial layer of gene regulation in recent years and regulate various biological processes such as carcinogenesis and metastasis. Megakaryoblastic leukemia 1 (MKL1), as a transcription coactivity factor, involved in cancer metastasis and cell differentiation. The precise mechanism of biological roles of HOTAIR and MKL1 in cancer cells remain unclear. As a member of the myocardin related transcription factor (MRTF) family, megakaryoblastic leukemia 1 (MKL1) is broadly expressed in many tissues [33] and functions as a co-activator of serum response factor (SRF), which played an important roles in the control of motile or contractile cell functions, especially during cancer metastasis, vascular smooth muscle cell and cardiac myocyte differentiation [33, 34]. MKL1/SRF complex could bind to a serum response element, which contains a core sequence known as the CArG-box, This element was characterized by the sequence CC(A/T)6GG, and often found in the promoter regions of targeting genes

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