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

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.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0216-3) contains supplementary material, which is available to authorized users.

Paeonol reverses promoting effect of the HOTAIR/miR‐124/Notch1 axis on renal interstitial fibrosis in a rat model

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“…In recent years, an increasing number of studies document that lncRNAs are essential regulator in various biological processes ( 18 – 20 ). In human cancer, lncRNAs have been demonstrated to serve pivotal roles in regulating cellular proliferation, apoptosis, migration and invasion ( 19 ).…”

Long noncoding RNA NEAT1 regulates glioma cells proliferation and apoptosis by competitively binding with miR-324-5p and upregulating KCTD20 expression

“…Many studies have shown that lncRNA exerts a crucial role in role in the development process, genomic imprinting, cellular homeostasis, and pluripotency of embryonic stem cells (7)(8)(9). Generally, the abnormally expressed lncRNAs participate in many biological mechanisms at the epigenetic, transcriptional, and posttranscriptional levels (10)(11)(12), such as cell proliferation, metabolism, apoptosis, migration and differentiation (13)(14)(15). Recently, a new regulatory mechanism indicates that the potential effect of lncRNAs is to inhibit the expression and biological functions of miRNAs(microRNA) as competing endogenous RNAs (ceRNA) (16,17).…”