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Background: Although MicroRNAs (mIRNAs) play Important roles In various biological processes, the biological functions of miRNAs are achieved through mRNAs. The aim of this study is to identify dysregulated miRNA/mRNA expression patterns in colorectal tumors. Methods: We examined 42 colorectal tumors [15 adenomas, 8 intramucosal cancers (IMCs), and 19 invasive colorectal cancers (CRCs)] with the microsatellite stable (MSS) phenotype (first cohort). The first cohort was used for genome-wide miRNA and mRNA expression arrays, whereas the second cohort (37 colorectal neoplasias) was used for validation analyses. Finally, we used 15 cases of "adenoma in/with carcinoma" to identify network patterns of miRNAs/mRNAs that were directly associated with neoplastic progression. In addition, simple regression analysis for array-based and RT-PCR analyses was performed to select candidate miRNA-mRNA pairs. Transfection of miRNA mimics was also performed to confirm whether target mRNA expression is affected by specific miRNAs. Results: Specific paired miRNA/mRNA networks, including hsa-miR-34a-5p/SLC12A2, hsa-miR-15b-5p/SLC12A2, hsa-miR-195-5p/SLC12A2, hsa-miRNA-502-3p/OLFM4, hsa-miRNA-6807-5p/ZG16, and hsa-miRNA 3064-5p/SH3BGRL3, were identified in samples of adenoma, IMC, and CRC with the MSS phenotype. In adenomatous lesions obtained from the same tumor with a carcinomatous lesion, we identified pairs of miRNA-130a-3p/HSPA8 and miRNA-22-3p/RP53 that were linked to multiple pathways. On the other hand, 2 pairs of miRNA/mRNA (miRNA-660-5p and miRNA-664a-5p/APP) were found in isolated carcinomatous glands. Ectopic expression of miRNA 3064-5p suppressed SH3BGRL3 expression. Conclusions: We found that networks based on specific pairs of miRNAs/mRNAs contribute to progression from adenomatous and carcinomatous lesions. Our results provide insights into the molecular tumorigenesis of colorectal tumors. [ABSTRACT FROM AUTHOR]

Methylation of normally unmethylated CpG-rich islands in or near the promoter region has been associated with transcriptional inactivation of tumor-suppressor and tumor-related genes in human cancers. However, so far, only a few studies have searched for DNA methylation in penile carcinoma (PC). On the other hand, human papillomavirus (HPV) has been reported to be associated with the pathogenesis of PC. To elucidate the methylation status of PC and HPV infection, the methylation status of eight genes (DAPK, FHIT, MGMT, p14, p16, RAR-beta, RASSF1A, and RUNX3), the incidences of the HPV status, and the expression of Fhit protein were examined in 25 PCs. The frequencies of methylation were: 28% for DAPK, 92% for FHIT, 20% for MGMT, 4% for p14, 24% for p16, 24% for RAR-beta, 12% for RASSF1A, and 44% for RUNX3. Negative expression of Fhit protein was observed in 22 of the 25 cancers (88%). Among those 22, 20 showed methylation of the FHIT gene. HPV-DNA was detected in three of the 25 cancers (12%). Methylation of FHIT gene was frequently found than HPV infection, therefore methylation of the FHIT gene is suggested to play an important role in the pathogenesis of penile squamous cell carcinoma. [ABSTRACT FROM AUTHOR]