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. 2020 Jul 9;20(3):2537–2556. doi: 10.3892/ol.2020.11835

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Copyright: © Gao et al.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Figure 2. — Roles of miR-33a and its target genes in gastric (top) and colorectal (bottom) cancer, and the underlying mechanisms. (A) miR-33a upregulation downregulates its target genes PIM1, CCND1 and CDK6, which inhibit proliferation and cell cycle. (B) miR-33a upregulation inhibits its target gene SNAI2, which further downregulates N-cadherin, vimentin, β-catenin, Snail and Slug, while upregulates E-cadherin, leading to the inhibition of EMT, migration and invasion. (C) LncRNA CASC15 inhibits miR-33a and further upregulates its target gene ZEB1, which upregulates N-cadherin and downregulates E-cadherin, promoting EMT and proliferation. (D) miR-33a upregulation inhibits its target gene PIM3, which further downregulates the downstream proteins p-p21 (upregulating p21), p-p27 (upregulating p27), p-MYC, C-MYC, CDK2, CDK4, cyclin B and cyclin E, leading to proliferation and cell cycle inhibition. (E) miR-33a upregulation downregulates its target gene ST8SIA1, inhibiting proliferation, invasion and chemoresistance. (F) miR-33a upregulation downregulates its target gene MTHFD2, inhibiting proliferation, migration and cell cycle. (G) miR-33a upregulation downregulates its target gene PIM1, inhibiting tumor growth. Red represents the factor causing miR-33a dysregulation; blue represents miR-33a; yellow represents the target genes of miR-33a; orange represents the downstream proteins; light green represents the signaling pathways and EMT processes; dark green represents the biological processes of cancer cells. miR, microRNA; EMT, epithelial-mesenchymal transition; p, phosphorylated; PIM1/3, Pim-1/3 proto-oncogene; CCND1, cyclin D1; CDK, cyclin-dependent kinase; SNAI2, Snail family transcriptional repressor 2; ZEB1, Zinc finger E-Box binding homeobox 1; ST8SIA1, ST8α-N-acetyl-neuraminide-α-2,8-sialyltransferase 1; MTHFD2, methylenetetrahydrofolate dehydrogenase 2.