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https://scholarbank.nus.edu.sg/handle/10635/195539
DC Field | Value | |
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dc.title | ELUCIDATING TRANSCRIPTIONAL ROLES OF SALL4 ISOFORMS IN SALL4HI HEPATOCELLULAR CARCINOMA | |
dc.contributor.author | KALPANA KUMARI | |
dc.date.accessioned | 2021-07-31T18:00:28Z | |
dc.date.available | 2021-07-31T18:00:28Z | |
dc.date.issued | 2021-01-20 | |
dc.identifier.citation | KALPANA KUMARI (2021-01-20). ELUCIDATING TRANSCRIPTIONAL ROLES OF SALL4 ISOFORMS IN SALL4HI HEPATOCELLULAR CARCINOMA. ScholarBank@NUS Repository. | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/195539 | |
dc.description.abstract | SALL4 is an onco-fetal transcription factor essential for survival of an aggressive subset of hepatocellular carcinoma (HCC). Typically, there are two SALL4 isoforms expressed and identified in HCC, namely SALL4A (full length) and SALL4B (alternate splice variant). This study shows that SALL4B isoform plays a novel role in upregulating the purine biosynthesis pathway and driving the process of hepatocellular oncogenesis. Additionally, SALL4hi HCC is vulnerable to SALL4B isoform-specific knockdown, leading to apoptosis and tumour regression. Furthermore, SALL4A degradation caused by IMIDs (thalidomide, lenalidomide, pomalidomide) does not affect HCC survival. Here, evidence is provided that SALL4B and upregulated purine metabolism can be uniquely targeted to inhibit tumorigenic properties of HCC. The mechanism of SALL4 activation in adult tissues and leading to cancer is not well understood. This study has identified cancer-specific novel clusters of enhancer elements present upstream of SALL4 promoter locus. The novel enhancer clusters also exhibit SALL4 transcription binding. Intriguingly, these enhancer clusters are sensitive to global perturbation of transcription coactivator CDK7. Additionally, CDK7 inhibition affects SALL4hi HCC with a selectivity of upto~20 fold. Moreover, transcriptional interruption through CDK7 leads to decreased expression of SALL4 regulated genes specifically. | |
dc.language.iso | en | |
dc.subject | SALL4, ISOFORM, HCC, METABOLISM, LIVER CANCER, ENHANCER, | |
dc.type | Thesis | |
dc.contributor.department | MEDICINE | |
dc.contributor.supervisor | Daniel G. Tenen | |
dc.contributor.supervisor | Leilei Chen | |
dc.description.degree | Ph.D | |
dc.description.degreeconferred | DOCTOR OF PHILOSOPHY (SOM) | |
Appears in Collections: | Ph.D Theses (Open) |
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KumariK.pdf | 3.29 MB | Adobe PDF | OPEN | None | View/Download |
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