Fig. 7: Hypothetical model for induction of proliferation blockage by ASK. ASncmtRNAs are produced in mitochondria. | Cell Death & Disease

Fig. 7: Hypothetical model for induction of proliferation blockage by ASK. ASncmtRNAs are produced in mitochondria.

From: Mitochondrial ncRNA targeting induces cell cycle arrest and tumor growth inhibition of MDA-MB-231 breast cancer cells through reduction of key cell cycle progression factors

Fig. 7

The antisense oligonucleotide Andes-1537 binds to the single-stranded loop region of ASncmtRNA-2, creating a substrate for RNase H, which cleaves the transcript in this region. After processing by Dicer, mitochondrial miRNA hsa-miR-4485, and possibly others, are released. By an unknown mechanism, possibly an indirect effect of hsa-miR-4485 expression, several nuclear-encoded miRNAs are increased, mainly hsa-miR-5096 and hsa-miR-3609. In conjunction, all these miRNAs block translation of key cell cycle progression factors, resulting in a drastic inhibition of proliferation. Triggering of apoptosis is mediated by miRNAs targeting survival factors such as survivin

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