scholarly journals RNA-Sequencing Based microRNA Expression Signature of Colorectal Cancer: The Impact of Oncogenic Targets Regulated by miR-490-3p

2021 ◽  
Vol 22 (18) ◽  
pp. 9876
Author(s):  
Yuto Hozaka ◽  
Yoshiaki Kita ◽  
Ryutaro Yasudome ◽  
Takako Tanaka ◽  
Masumi Wada ◽  
...  

To elucidate novel aspects of the molecular pathogenesis of colorectal cancer (CRC), we have created a new microRNA (miRNA) expression signature based on RNA-sequencing. Analysis of the signature showed that 84 miRNAs were upregulated, and 70 were downregulated in CRC tissues. Interestingly, our signature indicated that both guide and passenger strands of some miRNAs were significantly dysregulated in CRC tissues. These findings support our earlier data demonstrating the involvement of miRNA passenger strands in cancer pathogenesis. Our study focused on downregulated miR-490-3p and investigated its tumor-suppressive function in CRC cells. We successfully identified a total of 38 putative oncogenic targets regulated by miR-490-3p in CRC cells. Among these targets, the expression of three genes (IRAK1: p = 0.0427, FUT1: p = 0.0468, and GPRIN2: p = 0.0080) significantly predicted 5-year overall survival of CRC patients. Moreover, we analyzed the direct regulation of IRAK1 by miR-490-3p, and its resultant oncogenic function in CRC cells. Thus, we have clarified a part of the molecular pathway of CRC based on the action of tumor-suppressive miR-490-3p. This new miRNA expression signature of CRC will be a useful tool for elucidating new molecular pathogenesis in this disease.

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2418
Author(s):  
Xuezhen Zeng ◽  
Simon E. Ward ◽  
Jingying Zhou ◽  
Alfred S. L. Cheng

A drastic difference exists between the 5-year survival rates of colorectal cancer patients with localized cancer and distal organ metastasis. The liver is the most favorable organ for cancer metastases from the colorectum. Beyond the liver-colon anatomic relationship, emerging evidence highlights the impact of liver immune microenvironment on colorectal liver metastasis. Prior to cancer cell dissemination, hepatocytes secrete multiple factors to recruit or activate immune cells and stromal cells in the liver to form a favorable premetastatic niche. The liver-resident cells including Kupffer cells, hepatic stellate cells, and liver-sinusoidal endothelial cells are co-opted by the recruited cells, such as myeloid-derived suppressor cells and tumor-associated macrophages, to establish an immunosuppressive liver microenvironment suitable for tumor cell colonization and outgrowth. Current treatments including radical surgery, systemic therapy, and localized therapy have only achieved good clinical outcomes in a minority of colorectal cancer patients with liver metastasis, which is further hampered by high recurrence rate. Better understanding of the mechanisms governing the metastasis-prone liver immune microenvironment should open new immuno-oncology avenues for liver metastasis intervention.


BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Vaidotas Stankevicius ◽  
Gintautas Vasauskas ◽  
Danute Bulotiene ◽  
Stase Butkyte ◽  
Sonata Jarmalaite ◽  
...  

2017 ◽  
Vol 98 (1) ◽  
pp. 42-53 ◽  
Author(s):  
Queenie Wing-Lei Wong ◽  
Ming-An Sun ◽  
Shuk-Wa Lau ◽  
Chirag Parsania ◽  
Shaolong Zhou ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Jing Shi ◽  
Hui Liu ◽  
Hui Wang ◽  
Xiangqing Kong

Degenerative aortic stenosis, characterized by narrowing of the exit of the left ventricle of the heart, has become the most common valvular heart disease in the elderly. The aim of this study was to investigate the microRNA (miRNA) signature in degenerative AS. Through microarray analysis, we identified the miRNA expression signature in the tissue samples from healthy individuals (n=4) and patients with degenerative AS (n=4). Six miRNAs (hsa-miR-193a-3p, hsa-miR-29b-1-5p, hsa-miR-505-5p, hsa-miR-194-5p, hsa-miR-99b-3p, and hsa-miR-200b-3p) were overexpressed and 14 (hsa-miR-3663-3p, hsa-miR-513a-5p, hsa-miR-146b-5p, hsa-miR-1972, hsa-miR-718, hsa-miR-3138, hsa-miR-21-5p, hsa-miR-630, hsa-miR-575, hsa-miR-301a-3p, hsa-miR-636, hsa-miR-34a-3p, hsa-miR-21-3p, and hsa-miR-516a-5p) were downregulated in aortic tissue from AS patients. GeneSpring 13.1 was used to identify potential human miRNA target genes by comparing a 3-way comparison of predictions from TargetScan, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify potential pathways and functional annotations associated with AS. Twenty miRNAs were significantly differentially expressed between patients with AS samples and normal controls and identified potential miRNA targets and molecular pathways associated with this morbidity. This study describes the miRNA expression signature in degenerative AS and provides an improved understanding of the molecular pathobiology of this disease.


Tumor Biology ◽  
2013 ◽  
Vol 34 (6) ◽  
pp. 3501-3508 ◽  
Author(s):  
Xiaotang Yu ◽  
Xinchen Zhang ◽  
Tie Bi ◽  
Yanfang Ding ◽  
Jinyao Zhao ◽  
...  

2019 ◽  
Vol 79 (7) ◽  
pp. 1705-1713 ◽  
Author(s):  
Thomas E. Rohan ◽  
Tao Wang ◽  
Sheila Weinmann ◽  
Yihong Wang ◽  
Juan Lin ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Hui Wang ◽  
Jing Shi ◽  
Beibei Li ◽  
Qiulian Zhou ◽  
Xiangqing Kong ◽  
...  

Altered microRNA (miRNA, miR) expression has been related to many disease processes; however, the miRNA expression signature in calcific aortic valve disease (CAVD) is unclear. In this study, microarrays were used to determine the miRNA expression signature of tissue samples from healthy individuals (n=4) and patients with CAVD (n=4). TargetScan, PITA, and microRNAorg 3-way databases were used to predict the potential target genes. DIANA-miRPath was used to incorporate the aberrant miRNAs into gene pathways. miRNA microarrays identified 92 differentially expressed miRNAs in CAVD tissues. The principal component analysis (PCA) of these samples and the unsupervised hierarchical clustering analysis based on the 92 aberrantly expressed miRNAs noted that miRNA expression could be categorized into two well-defined clusters that corresponded to healthy control and CAVD. Bioinformatic analysis showed the miRNA targets and potential molecular pathways. Collectively, our study reported the miRNA expression signature in CAVD and may provide potential therapeutic targets for CAVD.


2011 ◽  
Vol 11 (1) ◽  
pp. 14 ◽  
Author(s):  
Jessica Carlsson ◽  
Sabina Davidsson ◽  
Gisela Helenius ◽  
Mats Karlsson ◽  
Zelmina Lubovac ◽  
...  

2021 ◽  
Vol 22 (11) ◽  
pp. 5763
Author(s):  
Vartika Bisht ◽  
Katrina Nash ◽  
Yuanwei Xu ◽  
Prasoon Agarwal ◽  
Sofie Bosch ◽  
...  

Integrative multiomics data analysis provides a unique opportunity for the mechanistic understanding of colorectal cancer (CRC) in addition to the identification of potential novel therapeutic targets. In this study, we used public omics data sets to investigate potential associations between microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing datasets. We identified multiple potential interactions, for example 5-aminovalerate interacting with Adlercreutzia; cholesteryl ester interacting with bacterial genera Staphylococcus, Blautia and Roseburia. Using public single cell and bulk RNA sequencing, we identified 17 overlapping genes involved in epithelial cell pathways, with particular significance of the oxidative phosphorylation pathway and the ACAT1 gene that indirectly regulates the esterification of cholesterol. These findings demonstrate that the integration of multiomics data sets from diverse populations can help us in untangling the colorectal cancer pathogenesis as well as postulate the disease pathology mechanisms and therapeutic targets.


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