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MICRORNAs INVOLVED IN THE REGULATION OF ENDOTHELIN-1 GENE EXPRESSION IN ENDOTHELIAL CELLS
by
Chen Li
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOCHEMISTRY AND MOLECULAR BIOLOGY)
August 2012
Copyright 2012 Chen Li
Object Description
| Title | MicroRNAs involved in the regulation of Endothelin-1 gene expression in endothelial cells |
| Author | Li, Chen |
| Author email | cli7@usc.edu;2009lichen@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Biochemistry and Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2012-08-03 |
| Date submitted | 2012-08-03 |
| Date approved | 2012-08-03 |
| Restricted until | 2014-08-03 |
| Date published | 2014-08-03 |
| Advisor (committee chair) | Kalra, Vijay K. |
| Advisor (committee member) |
Tokes, Zoltan A. Tahara, Stanley M. |
| Abstract | We showed that in human dermal microvascular endothelial cell line (HMEC-1), the stability of ET-1 mRNA was increased in response to PlGF treatment. We also observed that in PlGF treated HMEC-1, among several microRNAs (miRNA) which have a potential binding site on ET-1 mRNA and HIF- 1α mRNA, the levels of miR-648, miR-934 and miR-199a-5p were repressed significantly. Furthermore, we showed that among these microRNA candidates, miR-648 attenuated ET-1 mRNA expression, while antimiR-648 increased the expression of ET-1 mRNA under basal and PlGF treated conditions. To further validate this result, we constructed a pGL3-ET-1-3'UTR luciferase reporter. The activity of reporter construct was reduced by miR-648 mimic while antimiR-648 increased the reporter activity, both under basal and PlGF treated conditions. These studies showed miR-648 is involved in the regulation of ET-1 mRNA expression as a result of binding to the 3'UTR region of ET-1 mRNA. This study, for the first time, identified a novel miRNA regulator which functions in the expression of ET-1, and may play an important role in affecting pulmonary hypertension in SCD. |
| Keyword | endothelial cells; Endothelin-1; microRNA |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Li, Chen |
| Physical access | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@dots.usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-LiChen-1134.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | MICRORNAs INVOLVED IN THE REGULATION OF ENDOTHELIN-1 GENE EXPRESSION IN ENDOTHELIAL CELLS by Chen Li A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (BIOCHEMISTRY AND MOLECULAR BIOLOGY) August 2012 Copyright 2012 Chen Li |
