Asghar, Sidra
(2024)
Evaluation of snoRNA levels in HCC: a study explaining the role played by SNORA74D in HCC development, [Dissertation thesis], Alma Mater Studiorum Università di Bologna.
Dottorato di ricerca in
Oncologia, ematologia e patologia, 36 Ciclo.
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Abstract
Among non-coding genes small nucleolar RNA are recently getting attention in the field of prognosis and diagnosis of cancer including the Hepatocellular Carcinoma. The biological roles of snoRNA in HCC are, but no limited to, involvement in initiation, proliferation, metastasis, apoptosis, and cell cycle. Here in this study we are focusing on getting insight into the relationship between snoRNA and HCC. To this end we received sequenced tissue samples from patients with NASH and HCC. After performing initial bioinformatics analysis we found potential set of candidate snoRNAs i.e. SNORA74D, SNORA80D, and SNORA5C which were differentially expressed. We further verified these potential targets with qPCR analysis and found only SNORA74D to be significantly upregulated in HCC samples in comparison to NASH. In order to determine the mechanistic role we depleted HepG2 cell line from SNORA74D and found its potential role in cell survival and proliferation. TGIRT sequencing was also performed on SNORA74D depleted HepG2 samples to determine the prospective downstream effectors and regulators. Multiple protein coding genes and noncoding RNA are significantly dysregulated by knockdown of SNORA74D. Of note, we also characterized and discovered the presence of different isoforms of SNORA74D both in tissue samples and cell lines. The presence of different type of isoforms in cancer tissues compared with normal tissues further suggest potential involvement of SNORA74D in cancer development and progression.
Abstract
Among non-coding genes small nucleolar RNA are recently getting attention in the field of prognosis and diagnosis of cancer including the Hepatocellular Carcinoma. The biological roles of snoRNA in HCC are, but no limited to, involvement in initiation, proliferation, metastasis, apoptosis, and cell cycle. Here in this study we are focusing on getting insight into the relationship between snoRNA and HCC. To this end we received sequenced tissue samples from patients with NASH and HCC. After performing initial bioinformatics analysis we found potential set of candidate snoRNAs i.e. SNORA74D, SNORA80D, and SNORA5C which were differentially expressed. We further verified these potential targets with qPCR analysis and found only SNORA74D to be significantly upregulated in HCC samples in comparison to NASH. In order to determine the mechanistic role we depleted HepG2 cell line from SNORA74D and found its potential role in cell survival and proliferation. TGIRT sequencing was also performed on SNORA74D depleted HepG2 samples to determine the prospective downstream effectors and regulators. Multiple protein coding genes and noncoding RNA are significantly dysregulated by knockdown of SNORA74D. Of note, we also characterized and discovered the presence of different isoforms of SNORA74D both in tissue samples and cell lines. The presence of different type of isoforms in cancer tissues compared with normal tissues further suggest potential involvement of SNORA74D in cancer development and progression.
Tipologia del documento
Tesi di dottorato
Autore
Asghar, Sidra
Supervisore
Dottorato di ricerca
Ciclo
36
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
HCC, snoRNA, SNORA74D, SnoRNA isoforms
URN:NBN
Data di discussione
24 Giugno 2024
URI
Altri metadati
Tipologia del documento
Tesi di dottorato
Autore
Asghar, Sidra
Supervisore
Dottorato di ricerca
Ciclo
36
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
HCC, snoRNA, SNORA74D, SnoRNA isoforms
URN:NBN
Data di discussione
24 Giugno 2024
URI
Gestione del documento: