Matches in SemOpenAlex for { <https://semopenalex.org/work/W3040783610> ?p ?o ?g. }
- W3040783610 abstract "Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of malignancies with a nearly equal incidence and mortality rates in patients. Pancreatic stellate cells (PSCs) are critical players in PDAC microenvironment to promote the aggressiveness and pathogenesis of the disease. Dysregulation of microRNAs (miRNAs) have been shown to play a significant role in progression of PDAC. Earlier, we observed a PSC-specific downregulation of miR-29a in PDAC pancreas, however, the mechanism of action of the molecule in PSCs is still to be elucidated. The current study aims to clarify the regulation of miR-29a in PSCs and identifies functionally important downstream targets that contribute to tumorigenic activities during PDAC progression. Methods In this study, using RNAseq approach, we performed transcriptome analysis of paired miR-29a overexpressing and control human PSCs (hPSCs). Enrichment analysis was performed with the identified differentially expressed genes (DEGs). miR-29a targets in the dataset were identified, which were utilized to create network interactions. Western blots were performed with the top miR-29a candidate targets in hPSCs transfected with miR-29a mimic or scramble control. Results RNAseq analysis identified 202 differentially expressed genes, which included 19 downregulated direct miR-29a targets. Translational repression of eight key pro-tumorigenic and -fibrotic targets namely IGF-1, COL5A3, CLDN1, E2F7, MYBL2, ITGA6 and ADAMTS2 by miR-29a was observed in PSCs. Using pathway analysis, we find that miR-29a modulates effectors of IGF-1-p53 signaling in PSCs that may hinder carcinogenesis. We further observe a regulatory role of the molecule in pathways associated with PDAC ECM remodeling and tumor-stromal crosstalk, such as INS/IGF-1, RAS/MAPK, laminin interactions and collagen biosynthesis. Conclusions Together, our study presents a comprehensive understanding of miR-29a regulation of PSCs, and identifies essential pathways associated with PSC-mediated PDAC pathogenesis. The findings suggest an anti-tumorigenic role of miR-29a in the context of PSC-cancer cell crosstalk and advocates for the potential of the molecule in PDAC targeted therapies." @default.
- W3040783610 created "2020-07-16" @default.
- W3040783610 creator A5023054173 @default.
- W3040783610 creator A5025546679 @default.
- W3040783610 creator A5044524250 @default.
- W3040783610 creator A5046250069 @default.
- W3040783610 creator A5072416746 @default.
- W3040783610 creator A5080661780 @default.
- W3040783610 creator A5083403315 @default.
- W3040783610 creator A5086823444 @default.
- W3040783610 creator A5090606755 @default.
- W3040783610 date "2020-07-13" @default.
- W3040783610 modified "2023-09-26" @default.
- W3040783610 title "Global targetome analysis reveals critical role of miR-29a in pancreatic stellate cell mediated regulation of PDAC tumor microenvironment" @default.
- W3040783610 cites W144423133 @default.
- W3040783610 cites W1528751727 @default.
- W3040783610 cites W1958365843 @default.
- W3040783610 cites W1959222243 @default.
- W3040783610 cites W1976971569 @default.
- W3040783610 cites W1984208022 @default.
- W3040783610 cites W1985780641 @default.
- W3040783610 cites W1990776397 @default.
- W3040783610 cites W1995949259 @default.
- W3040783610 cites W2002877736 @default.
- W3040783610 cites W2004042953 @default.
- W3040783610 cites W2004267786 @default.
- W3040783610 cites W2008282782 @default.
- W3040783610 cites W2011543211 @default.
- W3040783610 cites W2013093033 @default.
- W3040783610 cites W2027140244 @default.
- W3040783610 cites W2027550738 @default.
- W3040783610 cites W2038302418 @default.
- W3040783610 cites W2048070053 @default.
- W3040783610 cites W2064871215 @default.
- W3040783610 cites W2066908088 @default.
- W3040783610 cites W2070779203 @default.
- W3040783610 cites W2076292517 @default.
- W3040783610 cites W2076921551 @default.
- W3040783610 cites W2083986341 @default.
- W3040783610 cites W2092095172 @default.
- W3040783610 cites W2113613985 @default.
- W3040783610 cites W2124249717 @default.
- W3040783610 cites W2134051389 @default.
- W3040783610 cites W2134903396 @default.
- W3040783610 cites W2135749247 @default.
- W3040783610 cites W2137459844 @default.
- W3040783610 cites W2138207763 @default.
- W3040783610 cites W2141549067 @default.
- W3040783610 cites W2163106706 @default.
- W3040783610 cites W2169456326 @default.
- W3040783610 cites W2220916195 @default.
- W3040783610 cites W2315407635 @default.
- W3040783610 cites W2417813882 @default.
- W3040783610 cites W2470530881 @default.
- W3040783610 cites W2510668565 @default.
- W3040783610 cites W2524907165 @default.
- W3040783610 cites W2529016964 @default.
- W3040783610 cites W2551414968 @default.
- W3040783610 cites W2555344458 @default.
- W3040783610 cites W2573530098 @default.
- W3040783610 cites W2579046240 @default.
- W3040783610 cites W2581500657 @default.
- W3040783610 cites W2588025094 @default.
- W3040783610 cites W2592304147 @default.
- W3040783610 cites W2606916679 @default.
- W3040783610 cites W2718870674 @default.
- W3040783610 cites W2744057663 @default.
- W3040783610 cites W2755156122 @default.
- W3040783610 cites W2774349794 @default.
- W3040783610 cites W2792088252 @default.
- W3040783610 cites W2792375985 @default.
- W3040783610 cites W2800431474 @default.
- W3040783610 cites W2803273701 @default.
- W3040783610 cites W2803837186 @default.
- W3040783610 cites W2807210051 @default.
- W3040783610 cites W2889646458 @default.
- W3040783610 cites W2889990912 @default.
- W3040783610 cites W2892619184 @default.
- W3040783610 cites W2897761225 @default.
- W3040783610 cites W2898789260 @default.
- W3040783610 cites W2899180023 @default.
- W3040783610 cites W2911225106 @default.
- W3040783610 cites W2919495822 @default.
- W3040783610 cites W2945882072 @default.
- W3040783610 cites W2947091225 @default.
- W3040783610 cites W2951582017 @default.
- W3040783610 cites W2958700011 @default.
- W3040783610 cites W2980387214 @default.
- W3040783610 cites W2982051641 @default.
- W3040783610 cites W2982189559 @default.
- W3040783610 cites W2982439020 @default.
- W3040783610 cites W2982703497 @default.
- W3040783610 cites W2987326932 @default.
- W3040783610 doi "https://doi.org/10.1186/s12885-020-07135-2" @default.
- W3040783610 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7359459" @default.
- W3040783610 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32660466" @default.
- W3040783610 hasPublicationYear "2020" @default.
- W3040783610 type Work @default.
- W3040783610 sameAs 3040783610 @default.
- W3040783610 citedByCount "12" @default.