Characterization of the MicroRNA Expression Profile of Cervical Squamous Cell Carcinoma Metastases

Objectives: MicroRNAs (miRNAs) are important regulators of many physiological and pathologicalprocesses, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecularmechanisms of metastatic cervical carcinoma by performing miRNA profiling.
Methods: Tissue samples werecollected from ten cervical squamous cancer patients who underwent hysterectomy and pelvic lymph node (PLN)dissection in our hospital, including four PLN-positive (metastatic) cases and six PLN-negative (non-metastatic)cases. A miRNA microarray platform with 1223 probes was used to determine the miRNA expression profiles ofthese two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positiveand PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAswith tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction(RT-PCR).
Results: Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive andPLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of themiRNAs (27/39) had tumor-associated target genes, and the expression levels of six of those (miR-126, miR-96,miR-144, miR-657, miR-490-5p, and miR-323-3p) were confirmed by quantitative (q)RT-PCR.
Conclusions:Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved incell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. Thesefindings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade bytargeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, itis likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or moleculartherapy.