Relationships between microRNA expressions and prognosis in patients with tongue squamous cell carcinoma and the mechanisms microRNA regulating tongue squamous cell carcinoma biological behavior / 北京大学学报(医学版)

ABSTRACT

SUMMARY Tonguesquamouscellcarcinoma(TSCC)isthemostcommontypeoforalcancerandis well known for its high rate of proliferation and lymph nodal metastasis.Exploring the underlying path-ways regulating TSCC could provide novel ideas for diagnosis and prognosis of TSCC patients,as well as molecular targets for treatment of TSCC.MicroRNAs (miRNAs)are small noncoding RNAs that inhibit gene expression through the 3′untranslated regions (3′UTRs)of their target messenger RNAs.They play crucial roles in numerous biological processes,including cancer progression.Although great efforts have been made,what role miRNAs may play in the early detection and diagnosis of TSCC is not fully under-stood .Recently,our team has performed a series of basic and clinical researches in an attempt to investi-gate the relationships between miRNA expressions and prognosis of patients with TSCC and the mecha-nisms under regulation of TSCC.The results showed that miR-1 95,miR-34a,miR-29b,miR-375 and miR-26a could inhibit TSCC cells progression and development via a sophisticated network of genes.Spe-cifically,the anti-tumor effects of miR-1 95 in TSCC may be partially mediated by its inhibition of Cy-clinD1 and Bcl-2 expression.The expression of miR-34a could inhibit migration and invasion of TSCC cell lines via targeting MMP9 and MMP1 4.The function of miR-29b may be through the miR-29b/Sp1 /PTEN/AKT axis.Overexpression of miR-375 inhibited Sp1 expression by targeting the 3′untranslated re-gion of the Sp1 transcript.MEG3 and miR-26a inhibited TSCC cell proliferation,cycle progression and promoted cell apoptosis and miR-26a could increase the MEG3 expression through reduction of the ex-pression of DNMT3B in TSCC.In light of the role of those miRNAs in diagnosis and prognosis of TSCC, we reported that decreased miR-1 95 and miR-375 expression was associated with poor overall survival rate of the TSCC patients,while miR-34a expression was negatively correlated with cervical lymph node me-tastases.Furthermore,combined low expression levels of miR-26a and MEG3 emerged as an independent prognostic factor for poor clinical outcomes in TSCC patients,suggesting that combined miR-26a and MEG3 expression might prove useful as an independent biomarker of clinical prognosis among TSCC pa-tients.