Long noncoding RNA MYOSLID promotes invasion and metastasis by modulating the partial epithelial-mesenchymal transition program in head and neck squamous cell carcinoma

Abstract

Background Partial epithelial mesenchymal transition (p-EMT) was found to play a potential role in the initial stage of metastasis in human head and neck squamous cell carcinoma (HNSCC). Some long noncoding RNAs (lncRNAs) have been reported to function as promoters or inhibitors of cancer metastasis. This study aimed to identify p-EMT-related lncRNAs in HNSCC. Methods Differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DEGs) in HNSCC obtained from The Cancer Genome Atlas (TCGA) were screened out by using the “edgeR” package. DE-lncRNAs in the Oral squamous cell carcinoma (OSCC) lncRNA microarray dataset GSE84805 were screened out by using the “limma” package. Slug-related lncRNAs were determined by Pearson correlation analysis (|Pearson correlation coefficient| ≥ 0.4, p < 0.01) based on TCGA. Survival analysis were performed for the overlapping DE-lncRNAs by using the “Survival” package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to predict the potential functions of MYOSLID. RT-qPCR and In Site Hybridization (ISH) were used to explore the MYOSLID expression and its clinical significance in HNSCC specimens. Immunohistochemical staining, siRNA, wound healing assay, transwell assay, and western blot were used to explore the biological function and potential molecular mechanisms. Results MYOSLID was identified as a Slug-related lncRNA and with prognostic value among the 9 overlapping DE-lncRNAs. GO and KEGG analyses revealed that MYOSLID was closely related to important biological processes and pathways that regulate cancer metastasis. The results of univariate and multivariate Cox regression analysis based on TCGA and HNSCC tissue microarray data suggested MYOSLID was an independent prognostic factor. MYOSLID expression in HNSCC was closely correlated with Slug, PDPN and LAMB3. The knockdown of MYOSLID in OSCC cell line significantly inhibited cell migration and invasion compared to those in the control cells. In addition, the knockdown of MYOSLID significantly reduced Slug, PDPN and LAMB3 expression levels. However, the knockdown of MYOSLID had no effect on the expression levels of the EMT biomarkers E-cadherin and Vimentin. Conclusions Our study revealed that MYOSLID expression was closely related to the p-EMT program in HNSCC, and it might be a new predictive biomarker for aggressive HNSCC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1254-4) contains supplementary material, which is available to authorized users.

The lncRNAs RP1-261G23.7, RP11-69E11.4 and SATB2-AS1 are a novel clinical signature for predicting recurrent osteosarcoma

“…We examined the correlation between the expression levels of the 42 differentially expressed lncRNAs and each differentially expressed mRNA using two-sided Pearson correlation coefficients and the z-test. The mRNAs positively or negatively correlated with the 42 lncRNAs were considered to be lncRNA-related mRNAs (|Pearson correlation coefficient| > 0.4 [16][17][18][19][20] and P-value <0.05). The lncRNA-mRNA co-expression network was then constructed using Cytoscape V.3.8.5 (https://cytoscape.org/).…”

LncRNA LINC00668 promotes cell proliferation, migration, invasion ability and EMT process in hepatocellular carcinoma by targeting miR-532-5p/YY1 axis

“…Increasing evidence has proved lncRNAs play a rather crucial role in pathophysiological process including tumorigenesis [6][7][8][9][10]. LncRNAs regulate biological behaviors including cell proliferation, cell apoptosis, cell metastasis etc., during tumorigenesis [11][12][13]. For instance, lncRNA NORAD promoted cell proliferation by competitively binding with miR-155-5p [14].…”

LINC00958 and HOXC13-AS as key candidate biomarkers in head and neck squamous cell carcinoma by integrated bioinformatics analysis

“…Studies have indicated that lncRNAs can serve as potential biomarkers for the early diagnosis and prognosis of multiple cancers, including HNSCC (Guglas et al, 2017;Li et al, 2019a). Recent reports have indicated that lncRNAs have multiple biological functions in HNSCC, including signaling regulation, invasion, metastasis, and potential prognostic biomarkers (Xiong et al, 2019;Zhang et al, 2019b). Qiu et al (2019) found that knockdown of RHPN1-AS1 inhibited cell migration, invasion and proliferation of HNSCC, indicating that RHPN1-AS1, acting as an oncogene, may be a potential diagnostic and therapeutic target in HNSCC.…”