Abstract
MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecular mechanisms of metastatic cervical carcinoma by performing miRNA profiling. Tissue samples were collected 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 of these two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positive and PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAs with tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive and PLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of the miRNAs (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. Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved in cell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. These findings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade by targeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, it is likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or molecular therapy.
Highlights
Cervical cancer is one of the most commonly diagnosed gynecological cancers
Several miRNAs have been found to function as either tumor metastasis promoters or suppressors (Asangani et al, 2008; Korpal et al, 2008; Li et al, 2009; Tsai et al, 2009), the exact role that miRNAs play in cervical cancer metastasis is only beginning to be uncovered
We describe our microarraybased investigation into the metastatic-related miRNA expression profile of cervical squamous cancer
Summary
Cervical cancer is one of the most commonly diagnosed gynecological cancers. The underlying molecular mechanisms that mediate the metastatic process leading to positive LN status in cervical cancer patients have yet to be fully elucidated. The recently identified regulatory mechanism of microRNA (miRNA)-mediated post-transcriptional gene expression has emerged as an intriguing possible regulator of cervical cancer metastasis. MiRNAs have already been implicated as regulators of many physiological and pathological processes, including development, proliferation, differentiation, apoptosis, and tumor progression and metastasis (Bartel et al, 2004; He et al, 2004; Esquela-Kerscher et al, 2006; Negrini et al, 2008; Tavazoie et al, 2008; Bartels et al, 2009; Garzon et al, 2009). The role of miRNAs in cervical cancer metastasis and the precise mechanism of its action in these tumor types remain largely unexplored
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