Browsing by Author "Bates, Alison"

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    The Role and Therapeutic Potential of miRNAs in Colorectal Liver Metastasis
    (Office of the Vice Chancellor for Research, 2015-04-17) Bansal, Ruchi; Sahu, Smiti Snigdha; Nabinger, Sarah C.; Guanglong, Jiang; Bates, Alison; Lee, Sangbin; Hiromi, Tanaka; Liu, Yunlong; Kota, Janaiah
    Colorectal cancer (CRC) is the third most common malignancy worldwide. Liver metastasis occurs in 60% of CRC patients and responds poorly to the available treatments making it the major cause of their mortality. MicroRNAs (miRNAs) are highly conserved, endogenously encoded small, non-coding RNA molecules that regulate global gene expression. The role of microRNAs in cancer pathogenesis, including CRC, has been well documented. However, in-depth miRNA expression analysis on a large cohort of CRC tumors is needed to identify the clinically relevant miRNAs and explore their potential to target liver metastases. To this purpose, we analyzed miRNA expression data of 406 CRC tumors from the publicly available colorectal cancer genome sequencing project and identified 58 miRNAs that were significantly downregulated. 10 miRNAs were selected for further analyses that were either known to target genes in cellular pathways or located within the commonly lost chromosomal loci associated with CRC liver metastases. Of these 10 miRNAs, miR-132, miR-378f, miR-605 and miR-1976 showed significant downregulation with >2 fold change (p>0.05) in primary and CRC liver metastasis tissues and in CRC cell lines. To investigate their anti-tumorigenic and metastatic properties, we transfected 3 different CRC cell lines (SW620, HCT-116 and CT-26) with miR-mimics and subjected them to cell proliferation, apoptosis and cell transformation assays. Ectopic expression of miR-378f, -605 and -1976 suppressed CRC cell proliferation, anchorage independent growth, migration and invasion and induced apoptosis. Interestingly, CRC patients with high miR-378f and miR-1976 had better survival compared to low expressing patients (p<0.044). Our in vitro data suggest the anti-tumorigenic/metastatic properties of miR-378f, -605 and -1976 in CRC. Further understanding of their functions and in vivo therapeutic evaluations may help in developing novel therapeutic strategies for this malignancy.
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    The Role and Therapeutic Potential of miRNAs in Colorectal Liver Metastasis
    (Springer Nature, 2019-11) Sahu, Smiti S.; Dey, Shatovisha; Nabinger, Sarah C.; Jiang, Guanglong; Bates, Alison; Tanaka, Hiromi; Liu, Yunlong; Kota, Janaiah; Medical and Molecular Genetics, School of Medicine
    Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide. Liver metastasis is the major cause of CRC patient mortality, occurring in 60% patients with no effective therapies. Although studies have indicated the role of miRNAs in CRC, an in-depth miRNA expression analysis is essential to identify clinically relevant miRNAs and understand their potential in targeting liver metastasis. Here we analyzed miRNA expressions in 405 patient tumors from publicly available colorectal cancer genome sequencing project database. Our analyses showed miR-132, miR-378f, miR-605 and miR-1976 to be the most significantly downregulated miRNAs in primary and CRC liver metastatic tissues, and CRC cell lines. Observations in CRC cell lines indicated that ectopic expressions of miR-378f, -605 and -1976 suppress CRC cell proliferation, anchorage independent growth, metastatic potential, and enhance apoptosis. Consistently, CRC patients with higher miR-378f and miR-1976 levels exhibited better survival. Together, our data suggests an anti-tumorigenic role of these miRNAs in CRC and warrant future in vivo evaluation of the molecules for developing biomarkers or novel therapeutic strategies.