HE440 Lecture Notes - Lecture 11: Cyclin-Dependent Kinase, Tumor Microenvironment, Non-Coding Rna
Document Summary
Long non-coding rnas: 3" end of cdkn2a (cyclin dependent kinase inhibitors) encodes cdkn2bas an antisense non-coding rna in the ink4 locus (anril, anril is deregulated in many cancers - lung, breast, melanoma, nasopharyngeal, glioma. In normal cells: e2f induces anril to suppressed expression of the cell cycle inhibitors. Cdkn2a and cdknb: restart the cell cycle after dna repair. In cancer: hijacked and overexpression of anril prevents cell cycle halt during. Dna damage: promotes tumour progression, anril is related to progression and poor prognosis, anril acts by increasing cell proliferation and reprograming energy metabolism towards glucose update. Metabolism: metabolic enzymes mutations play a key role in oncogenesis, prominent example: isocitrate dehydrogenase (idh, two isoforms idh1 (cytosol) and idh2 (mitochondrion, regulate the interconversion of isocitrate and alpha ketoglutarate by oxidative decarboxylation. Idh1 mutation often at a specific location in some brain cancers (glioma/glioblastoma) Idh2 mutation often found in acute myeloid leukemia.
