AUTHOR=Sugai Tamotsu , Osakabe Mitsumasa , Niinuma Takeshi , Sugimoto Ryo , Eizuka Makoto , Tanaka Yoshihito , Yanagawa Naoki , Otsuka Koki , Sasaki Akira , Matsumoto Takayuki , Suzuki Hiromu 

TITLE=Genome-Wide Analysis of microRNA and mRNA Expression in Colorectal Intramucosal Neoplasia and Colorectal Cancer With a Microsatellite-Stable Phenotype Based on Adenoma-Carcinoma Sequences

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.831100

DOI=10.3389/fonc.2022.831100

ISSN=2234-943X

ABSTRACT=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.