Therapeutic Inhibitors of LIN28/let-7 Pathway in Ovarian Cancer
Abstract
There are two major goals of this research project: 1) To define how specific TUTases function in ovarian cancer cells that are either LIN28B-positive or LIN28A/LIN28B-double negative, 2) To perform a pilot small molecule screen in LIN28-positive ovarian cancer cells to identify compounds that restore expression of the tumor suppressor let-7 microRNA family in LIN28-positive ovarian cancer cells. Mechanistically, we envision that these molecules would inhibit LIN28 and its interacting TUTase(s). During this reporting period, we have generated loss-of-function cell lines with reduced TUTase expression singly or in combination, using an RNAi approach. These cells have been analyzed with the respect to cell proliferation and migration. Also, high quality RNA was isolated from multiple loss-of-function cell lines to perform global microRNA profiling to determine if LIN28B requires a TUTase(s) to repress let-7 microRNA biogenesis and if TUTases regulate microRNA expression in the absence of LIN28A/LIN28B expression. In addition, we have generated numerous stable cell lines with distinct let-7 reporters for use in our pilot screen for both LIN28A-positive (OVK-18 and Igrov-1) and LIN28B positive cell lines (TOV-112D).
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2015
- Accession Number
- AD1001283
Entities
People
- John P. Hagan
- Julien Balzeau
- Miriam Menezes
- Siyu Cao
Organizations
- University of Texas Health Science Center at Houston