Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA‐1 in Met expression

Abstract

Emerging evidence suggests that microRNA (miRNA) expression signatures in cancer may have important diagnostic, prognostic, and therapeutic value, but there is no data on miRNA expression in chordoma. The purpose of this study was to identify the role of miRNAs in human chordoma. We analyzed miRNA expression in chordoma-derived cell lines and chordoma tissue by using miRNA microarray technology with unsupervised hierarchical clustering analysis. The relative expression levels of these miRNAs were confirmed by real-time quantitative RT-PCR and Northern blot analysis. To characterize the potential role of miRNA-1, miRNA-1 was stably transfected into a chordoma cell line, UCH1. The expression of miRNA-1 targeted gene Met in chordoma tissues was also studied. We observe that human chordoma tissues and cell lines can be distinguished from normal muscle tissue by comparing miRNA expression profiles. Several miRNAs were differentially expressed in chordoma cell lines compared to controls, and similar expression patterns were found in primary chordoma tissues. Importantly, we were able to show for the first time, to our knowledge, that expression of miRNA-1 and miRNA-206, two miRNAs implicated in a number of other cancer types, were markedly decreased in both chordoma tissues and cell lines. When chordoma cell lines were transfected with miRNA-1, downregulation of known miRNA-1 targets was observed. These targets included Met and HDAC4-two genes that were observed to be overexpressed in chordoma. Our results demonstrate that some miRNAs are differentially expressed in chordoma and, in particular, miRNA-1 may have a functional effect on chordoma tumor pathogenesis. ß

Prognostic implication of MET overexpression in myxofibrosarcomas: an integrative array comparative genomic hybridization, real-time quantitative PCR, immunoblotting, and immunohistochemical analysis

“…[15][16][17]21,23,[42][43][44] More recently, several small non-coding microRNAs, including miR-34b, miR-34c, miR-199a*, miRNA-1, and miRNA-206, have been proved to upregulate MET protein expression in a variety of cancers by either targeting MET mRNA for degradation or repressing its translation post-transcriptionally. 43,[45][46][47] These microRNAs may constitute a novel and critical mechanistic basis to modulate MET expression in tumor cells. Through binding of activated HGF to its extracellular domain, MET undergoes oligomerization with subsequent phosphorylation of multiple tyrosine residues at the intracellular domains of the b subunit, thereby modulating its internalization, catalytic activity, and docking of adaptor proteins.…”

Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease

“…downregulated and upregulated myomiRs respectively, and Table 6 lists validated myomiR targets related to enhanced cancer progression. An excellent review by Nohata et al [84] (2012) reported changes in the expression of the miR1/ 133a and miR206/133b cistron clusters in numerous cancers, typically finding reduced expression of different combinations of myomiRs, such as in lung cancer [85] , colorectal cancer [86,87] , rhabdomyosarcoma [88,89] , chordoma [90] osteosarcoma [91] , muscleinvasive bladder cancer [92] , bladder cancer (transitional cell carcinoma) (TCC) [93] , ESCC [94] , breast cancer [95] and prostate cancer [9597] . In different cancers (Figure 3) deregulation typically involves downregulation of one or more myomiR isomers, indicating they normally function as tumor suppressors in the tissues, limiting Metastatic CRC [301] Notch3, Hes1, Bcl-2 and MMP-9; Exogenous upregulation of miR-206 expression;…”

MicroRNA profiling and bioinformatics analyses reveal the potential roles of microRNAs in chordoma

“…Dysregulation of miRNAs that target the expression of oncogenes or tumor suppressor genes may therefore influence a number of essential biological functions, including cancer initiation and progression (6,7). The role of miRNAs in chordoma has been studied when compared with muscle tissue or adult nucleus pulposus tissues (8)(9)(10). Certain miRNAs are differentially expressed in chordoma and, in particular, miR-1 and miR-31 may have a functional impact on chordoma tumor pathogenesis (8,9).…”

“…The role of miRNAs in chordoma has been studied when compared with muscle tissue or adult nucleus pulposus tissues (8)(9)(10). Certain miRNAs are differentially expressed in chordoma and, in particular, miR-1 and miR-31 may have a functional impact on chordoma tumor pathogenesis (8,9). Nevertheless, the unique expression profiles of miRNAs and their downstream signaling pathways in chordoma remain incompletely characterized.…”