Roles of micro-RNAs in apoptosis-induced proliferation

Yu, Mengyuan (2023). Roles of micro-RNAs in apoptosis-induced proliferation. University of Birmingham. Ph.D.

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Abstract

Apoptosis is an essential process to maintain the balance between cell death and cell division in multicellular organisms. Interestingly, evidence has emerged that caspases, the key proteases executing apoptosis, can also induce additional divisions of cells next to apoptotic cells. This process has been defined as apoptosis-induced proliferation (AiP). Recent studies have revealed that AiP is a potential contributor to tumour repopulation and tissue regeneration. Activation of the initiator caspase Dronc, a Drosophila ortholog of the mammalian caspase-9, and c-Jun N-terminal kinase (JNK) is a key process mediating AiP. JNK further triggers production and release of mitogen signals such as Dpp/TGF-β, Wg/Wnt and Spi/EGF leading to AiP. Additionally, a feedback amplification loop involving a transcriptional regulation of the proapoptotic genes hid and rpr has been identified to regulate JNK during AiP. However, our understanding of the molecular mechanisms underlying AiP is still very limited. My PhD project focuses on microRNAs (miRNAs), a class of small non-coding RNAs that regulate gene expression. I found that the miR-309-6 cluster, which contains 8 miRNAs including miR-6-1, miR-6-2, miR-6-3, miR-5, miR-4, miR-286, miR-3, miR-309, is required for AiP. Intriguingly, miR-286 and miR-6 in this cluster have distinct functions in regulating AiP via different mechanisms. Moreover, expression of miR-286, but not miR-6, is regulated during AiP in a Dronc-dependent manner. By combining in silico analysis and experimental validation, I have identified a potential target of miR-286 that regulates AiP. Therefore, my study has discovered novel roles of miRNAs in the regulation of AiP.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):