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CRISPRa screening identifies lncRNAs regulating tumor response to CD8+ T cell cytotoxicity

Zhao, Yueshan (2022) CRISPRa screening identifies lncRNAs regulating tumor response to CD8+ T cell cytotoxicity. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Human genomes contain abundant non-coding RNAs which may play critical roles in all aspects of functions through diverse mechanisms in cancer cells, among which long non-coding RNAs (lncRNAs) have been reported to regulate cell proliferation, metastasis, and drug resistance. Recent studies have shown lncRNAs can act as biomarkers for immunotherapy efficacy in patients. However, the relationship between lncRNAs and immune response in cancer treatment is not well explored currently. In this thesis, we performed genome-wide CRISPR activation screening in melanoma cells with human CD8+ T cells co-culture treatment. The screening identified top ranked genes including IL10RB-DT and LINC01198 that can result in resistance/sensitivity to T cells cytotoxicity respectively. IL10RB-DT/LINC01198 expression demonstrated significantly negative/positive correlation with immune cell infiltration and overall survival of patients with melanoma and breast cancer. Additionally, we performed RNA-seq in activated or inhibited IL10RB-DT and LINC01198 melanoma and breast cancer cell lines by single sgRNA transfection or siRNA treatment. Pathway analysis revealed that these two lncRNAs were associated with the regulation of Type I and Type II interferon related pathways in both activation and knockdown models. These results demonstrated the feasibility of in vitro high-throughput screening of potential lncRNAs associated with immune response and suggested novel targets for cancer immunotherapy.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Zhao, Yueshanyuz183@pitt.eduyuz183
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairYang, Dadyang@pitt.edudyang
Committee MemberZhang, Minmiz45@pitt.edumiz45
Committee MemberGibbs, Robertgibbsr@pitt.edugibbsr
Date: 7 April 2022
Date Type: Publication
Defense Date: 31 March 2022
Approval Date: 7 April 2022
Submission Date: 5 April 2022
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 52
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: CRISPRa screening, lncRNA, T cell cytotoxicity
Date Deposited: 07 Apr 2022 19:00
Last Modified: 07 Apr 2022 19:00
URI: http://d-scholarship.pitt.edu/id/eprint/42487

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