Dysregulation of miR-200 family microRNAs and epithelial-mesenchymal transition markers in oral squamous cell carcinoma

Arunkumar, Ganesan; Rao, Arunagiri Kuha Deva Magendhra; Manikandan, Mayakannan; Rao, Harikrishnan Prasanna Srinivasa; Shanmugam, Subbiah; Ilangovan, R.; Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan

doi:10.3892/ol.2017.7296

Cited by 54 publications

(64 citation statements)

References 42 publications

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“…This suggests that ZEB2 represents a major target for P. gingivalis-induced remodeling of the gingival epithelial cell transcriptional program, and this could have major consequences for homeostasis. Increased ZEB2 expression has been reported in esophageal and oral squamous cell cancer and is associated with poor prognosis (59)(60)(61). In addition, ZEB2 has recently been shown to control inflammatory responses, including the production of IL-6, a cytokine with a role in periodontal bone resorption (62).…”

Section: Discussionmentioning

confidence: 99%

Streptococcus gordonii programs epithelial cells to resist ZEB2 induction by Porphyromonas gingivalis

Ohshima

Wang

Fitzsimonds

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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The polymicrobial microbiome of the oral cavity is a direct precursor of periodontal diseases, and changes in microhabitat or shifts in microbial composition may also be linked to oral squamous cell carcinoma. Dysbiotic oral epithelial responses provoked by individual organisms, and which underlie these diseases, are widely studied. However, organisms may influence community partner species through manipulation of epithelial cell responses, an aspect of the host microbiome interaction that is poorly understood. We report here thatPorphyromonas gingivalis, a keystone periodontal pathogen, can up-regulate expression of ZEB2, a transcription factor which controls epithelial–mesenchymal transition and inflammatory responses. ZEB2 regulation byP. gingivaliswas mediated through pathways involving β-catenin and FOXO1. Among the community partners ofP. gingivalis,Streptococcus gordoniiwas capable of antagonizing ZEB2 expression. Mechanistically,S. gordoniisuppressed FOXO1 by activating the TAK1-NLK negative regulatory pathway, even in the presence ofP. gingivalis. Collectively, these results establishS. gordoniias homeostatic commensal, capable of mitigating the activity of a more pathogenic organism through modulation of host signaling.

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Section: Discussionmentioning

confidence: 99%

Streptococcus gordonii programs epithelial cells to resist ZEB2 induction by Porphyromonas gingivalis

Ohshima

Wang

Fitzsimonds

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…A myriad of cellular processes, including differentiation, development, proliferation, and apoptosis, are dictated by microRNAs (miRNAs), which are small segments of non-coding RNAs [9,10]. By negatively regulating gene expression at the post-transcriptional level, these single-stranded RNAs can inhibit gene translation and trigger the direct degradation of target messenger RNAs (mRNAs) [11].…”

Section: Introductionmentioning

confidence: 99%

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1

Nan

Zhong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Emerging evidence suggests that the propagation of oral squamous cell carcinoma (OSCC) is influenced by the abnormal expression of microRNAs (miRNAs). This study aimed to characterize the involvement of miR-182-5p in OSCC by targeting the calcium/ calmodulin-dependent protein kinase II inhibitor CAMK2N1. Methods: miR-182-5p expression was quantified in OSCC tissues and cell lines with reverse transcription polymerase chain reaction (RT-PCR). Cell colony formation, Cell Counting Kit-8 (CCK-8), Ki-67, and nude mouse xenograft assays were used to characterize the role of miR-182-5p in the proliferation of OSCC. A miR-182-5p target gene was identified with western blotting, RT-PCR, and luciferase activity assays. OSCC patient survival based on CAMK2N1 expression was also analyzed. Results: miR-182-5p was up-regulated in in vitro cell lines and in vivo clinical OSCC samples. CCK-8, colony formation, and Ki-67 assays revealed that miR-182-5p promoted the growth and proliferation of OSCC cells. miR-182-5p directly targeted CAMK2N1, as evidenced by luciferase assays and target prediction algorithms. CAMK2N1 operated as a tumor suppressor gene in patients with OSCC. Down-regulating miR-182-5p expression in the CAL-27 cell line restored CAMK2N1-mediated OSCC cell proliferation. miR-182-5p expression inhibited the activation of AKT, ERK1/2, and NF-κB. Mice injected with CAL-27 cells transfected with miR-182-5p-inhibitor demonstrated a significant increase in tumor size and weight and increased CAMK2N1 mRNA and protein expression compared with the miR-negative control group. Conclusion: The miR-182-5p-CAMK2N1 pathway can be potentially targeted to regulate the proliferation of OSCC cells.

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“…However, OIP5 was targeted by stemness regulatory miR-143/145, EMT associated miR-200 family and oral cancer-specific tumor suppressor let-7 family. In oral cancer, the expression of OIP5 may not be regulated at the posttranscription level as the miR-143/145, miR-200 and let-7 family microRNAs were reported to be downregulated in oral cancer [9,11,14]. These results suggest that with OIP5 gene, lncRNA OIP5-AS1 may play a synergistic role in oral tumorigenesis.…”

Section: Discussionmentioning

confidence: 94%

“…In addition, Epithelial-mesenchymal transition (EMT), a transdifferentiating mechanism that directs changes in cell states along the epithelial versus mesenchymal axes is a major event in oral cancer progression and metastasis. EMT confers epithelialmesenchymal plasticity upon epithelial cells and the cellular transformation process is orchestrated by a group of transcription factors (TFs), such as the SNAIL, TWIST, and ZEB families [9]. Recently, we reported the role of natural antisense transcript (NAT) for EMT signaling in oral tumors [9].…”

Section: Introductionmentioning

confidence: 99%

“…EMT confers epithelialmesenchymal plasticity upon epithelial cells and the cellular transformation process is orchestrated by a group of transcription factors (TFs), such as the SNAIL, TWIST, and ZEB families [9]. Recently, we reported the role of natural antisense transcript (NAT) for EMT signaling in oral tumors [9]. Therefore, the pathways of carcinogenesis in Indian population might be different from other population which might lead through chromosome instability, telomere lengthening, hormonal activation, environmental factors, chromatin modification, epigenetic changes and dysregulation of non-coding RNAs.…”

Section: Introductionmentioning

confidence: 99%

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LncRNAOIP5-AS1is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors

Arunkumar

Anand

Raksha

et al. 2018

Preprint

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LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors. Correspondence to: A. K. Munirajan, email: akmunirajan@gmail.com; akmunirajan@unom.ac.in. GanesanAll rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.Thecopyright holder for this preprint . http://dx.doi.org/10.1101/285270 doi: bioRxiv preprint first posted online Mar. 19, 2018; 2 AbstractLong non-coding RNAs (lncRNAs) play an important role in the regulation of key cellular processes in early development and in cancer. LncRNA Oip5-as1 facilitates stem cell self-renewal in mouse by sponging mmu-miR-7 and modulating NANOG level, yet its role in cancer is less understood. We analyzed OIP5-AS1 expression in oral tumors and in TCGA datasets. We observed overexpression of OIP5-AS1 in oral tumors (P<0.001) and in tumors of epithelial origin from TCGA. OIP5-AS1 expression was strongly associated with undifferentiated tumors (P=0.0038). In silico analysis showed miR-7 binding site is conserved in mouse and human OIP5-AS1. However, human NANOG 3`-UTR lost the binding site for hsa-miR-7a-3. Therefore, we screened for other miRNAs that can be sponged

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Dysregulation of miR-200 family microRNAs and epithelial-mesenchymal transition markers in oral squamous cell carcinoma

Cited by 54 publications

References 42 publications

Streptococcus gordonii programs epithelial cells to resist ZEB2 induction by Porphyromonas gingivalis

Streptococcus gordonii programs epithelial cells to resist ZEB2 induction by Porphyromonas gingivalis

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1

LncRNAOIP5-AS1is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors

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