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. 2023 Mar 22;83(10):1563–1572. doi: 10.1158/0008-5472.CAN-23-0296

Figure 1.

Figure 1. The miRNA regulatory pathway, associated cancers and the effect of KRASMUT on miRNA processing. A, Nuclear miRNA processing and cancers associated with mutations in the microprocessor. B, Cytoplasmic miRNA processing and cancers associated with mutations in cytoplasmic factors. C, KRASMUT-induced effects on miRNA biogenesis, processing, and function. (i) increased oncomirs and decreased tumor suppressive miRNAs via KIMAT1 and DHX9. (ii) Decreased miRNA export. (iii) Decreased cytoplasmic DICER processing function. (iv) Decreased exosomal miRNA secretion and increased PB localization of AGO2. (v) Inhibition of AGO2 miRNA processing function. (vi) Inhibition of AGO2 slicing activity. (vii) Upregulation of SG formation and increased cell survival and therapy resistance. (viii) Upregulation of UPR and shift from tubular to cisternal ER, causing decreased PB fission events and decreased PB numbers.

The miRNA regulatory pathway, associated cancers, and the effect of KRASMUT on miRNA processing. A, Nuclear miRNA processing and cancers associated with mutations in the microprocessor. B, Cytoplasmic miRNA processing and cancers associated with mutations in cytoplasmic factors. C, KRASMUT-induced effects on miRNA biogenesis, processing, and function. i, Increased oncomirs and decreased tumor suppressive miRNAs via KIMAT1 and DHX9. ii, Decreased miRNA export. iii, Decreased cytoplasmic DICER processing function. iv, Decreased exosomal miRNA secretion and increased PB localization of AGO2. v, Inhibition of AGO2 miRNA processing function. vi, Inhibition of AGO2 slicing activity. vii, Upregulation of SG formation and increased cell survival and therapy resistance. viii, Upregulation of UPR and shift from tubular to cisternal ER, causing decreased PB fission events and decreased PB numbers.