Browsing by Author "Guanglong, Jiang"

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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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    Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent
    (Springer Nature, 2023-09-14) Kumar, Brijesh; Khatpe, Aditi S.; Guanglong, Jiang; Batic, Katie; Bhat-Nakshatri, Poornima; Granatir, Maggie M.; Addison, Rebekah Joann; Szymanski, Megan; Baldridge, Lee Ann; Temm, Constance J.; Sandusky, George; Althouse, Sandra K.; Cote, Michele L.; Miller, Kathy D.; Storniolo, Anna Maria; Nakshatri, Harikrishna; Surgery, School of Medicine
    The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to ductal epithelial cells in normal breasts of women of African ancestry compared to those of European ancestry. In this study, we demonstrate that these cells have properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRα and transdifferentiate into adipogenic and osteogenic lineages. PROCR + /ZEB1 + /PDGFRα+ (PZP) cells are enriched in normal breast tissues of women of African compared to European ancestry. PZP: epithelial cell communication results in luminal epithelial cells acquiring basal cell characteristics and IL-6-dependent increase in STAT3 phosphorylation. Furthermore, level of phospho-STAT3 is higher in normal and cancerous breast tissues of women of African ancestry. PZP cells transformed with HRasG12V ± SV40-T/t antigens generate metaplastic carcinoma suggesting that these cells are one of the cells-of-origin of metaplastic breast cancers.