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MicroRNAs in apoptosis, autophagy and necroptosis.

Su Z, Yang Z, Xu Y, Chen Y, Yu Q - Oncotarget (2015)

Bottom Line: Numerous miRNAs regulate programmed cell death including apoptosis, autophagy and necroptosis.We summarize how miRNAs regulate apoptotic, autophagic and necroptotic pathways and cancer progression.We also discuss how miRNAs link different types of cell death.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Medical School, Southeast University, Nanjing, Jiangsu 210009, China.

ABSTRACT
MicroRNAs (miRNAs) are endogenous 22 nt non-coding RNAs that target mRNAs for cleavage or translational repression. Numerous miRNAs regulate programmed cell death including apoptosis, autophagy and necroptosis. We summarize how miRNAs regulate apoptotic, autophagic and necroptotic pathways and cancer progression. We also discuss how miRNAs link different types of cell death.

No MeSH data available.


Related in: MedlinePlus

miRNAs regulate the major cascades of autophagyAutophagy includes at least six successive events: induction, vesicle nucleation (or phagophore formation), vesicle elongation and autophagosome formation, ATG protein and lipid retrieval, fusion of the autophagosome to an lysosome/endosome and autolysosome formation, and autolysosome cargo degradation. The ULK complex, which is composed of ULK1/2, ATG13, FIP200, and ATG101, is activated by the inhibition of mTORC1 and initiates the autophagy program. The class III PI3K complex, which is composed of Beclin-1, class III PI3K (i.e., Vps34), p150 (i.e., Vps15), ATG14L, and certain regulatory factors, is essential for vesicle nucleation. Two ubiquitin-like protein conjugation systems form two important complexes (the LC3-II-PE complex and the ATG5-ATG12-ATG16L1 complex) that are critical for vesicle elongation. The transmembrane proteins VMP1 and ATG9 also play a role in nascent autophagosome formation. The major miRNAs involved in the regulation of key members of autophagy cascades are shown in the diagram in dark blue. mTORC1, mammalian target of rapamycin complex 1; ULK, UNC-51-like kinase; ATG, autophagy-related gene; FIP200, focal adhesion kinase family-interacting protein of 200 kDa; UVRAG, UV radiation resistance-associated gene; Rubicon, RUN domain protein as Beclin-1 interacting and cysteine-rich containing; PE, phosphatidylethanolamine; VMP1, vacuole membrane protein 1; PI3K, phosphatidylinositol-3 kinase. Pro-LC3, primary translation product of LC3; LC3-I, cytosolic form of LC3 that is cleaved from Pro-LC3 by ATG4; LC3-II, lipidated form of LC3 that is conjugated to PE. See the text for details.
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Figure 2: miRNAs regulate the major cascades of autophagyAutophagy includes at least six successive events: induction, vesicle nucleation (or phagophore formation), vesicle elongation and autophagosome formation, ATG protein and lipid retrieval, fusion of the autophagosome to an lysosome/endosome and autolysosome formation, and autolysosome cargo degradation. The ULK complex, which is composed of ULK1/2, ATG13, FIP200, and ATG101, is activated by the inhibition of mTORC1 and initiates the autophagy program. The class III PI3K complex, which is composed of Beclin-1, class III PI3K (i.e., Vps34), p150 (i.e., Vps15), ATG14L, and certain regulatory factors, is essential for vesicle nucleation. Two ubiquitin-like protein conjugation systems form two important complexes (the LC3-II-PE complex and the ATG5-ATG12-ATG16L1 complex) that are critical for vesicle elongation. The transmembrane proteins VMP1 and ATG9 also play a role in nascent autophagosome formation. The major miRNAs involved in the regulation of key members of autophagy cascades are shown in the diagram in dark blue. mTORC1, mammalian target of rapamycin complex 1; ULK, UNC-51-like kinase; ATG, autophagy-related gene; FIP200, focal adhesion kinase family-interacting protein of 200 kDa; UVRAG, UV radiation resistance-associated gene; Rubicon, RUN domain protein as Beclin-1 interacting and cysteine-rich containing; PE, phosphatidylethanolamine; VMP1, vacuole membrane protein 1; PI3K, phosphatidylinositol-3 kinase. Pro-LC3, primary translation product of LC3; LC3-I, cytosolic form of LC3 that is cleaved from Pro-LC3 by ATG4; LC3-II, lipidated form of LC3 that is conjugated to PE. See the text for details.

Mentions: The ULK complex, which is composed of ULK1, ULK2, ATG13, ATG101, and the focal adhesion kinase family-interacting protein of 200 kDa (FIP200), is crucial for autophagy induction. Mammalian target of rapamycin complex 1 (mTORC1) binds to and inactivates ULK1 and ULK2. The dissociation of mTORC1 from the ULK complex leads to ULK1/2 activation and the subsequent phosphorylation of FIP200 and ATG13, which initiates phagophore formation [73]. The PI3K complex, which is essential for vesicle nucleation, is composed of class III PI3K, Beclin-1, ATG14L, p150, and several regulators including Ambra1, Bif-1, UV radiation resistance-associated gene (UVRAG), Bcl-2, Bcl-xL, and the Run domain protein Rubicon [74]. The LC3 and ATG12 ubiquitin-like protein conjugation systems are responsible for vesicle elongation. In the LC3 conjugation system, ATG4 cleaves pro-LC3 into cytosolic LC3-I, which successively binds to ATG7 and ATG3. LC3-I is processed by these two autophagy-related proteins and is then coupled to phosphatidylethanolamine (PE) to become a membrane-bound PE-conjugated LC3, LC3-II. In the ATG12 conjugation system, ATG12 successively binds to ATG7, ATG10, and ATG5 and finally conjugates with autophagy-related 16-like 1 (ATG16L1) to form the ATG16L1-ATG5-AGT12 complex [74, 75]. These two ubiquitination-like systems are closely connected. For example, the ATG16L1-ATG5-AGT12 complex is localized to the phagophore and potentially acts as a novel E3-like enzyme to determine the sites at which LC3 conjugates with PE [76]. VMP1 is thought to function by recruiting Beclin-1 and other components in the class III PI3K complex to the phagophore, whereas ATG9 is thought to contribute to the delivery of membrane particles to the forming autophagosome [74]. The major autophagy cascades are depicted in Figure 2.


MicroRNAs in apoptosis, autophagy and necroptosis.

Su Z, Yang Z, Xu Y, Chen Y, Yu Q - Oncotarget (2015)

miRNAs regulate the major cascades of autophagyAutophagy includes at least six successive events: induction, vesicle nucleation (or phagophore formation), vesicle elongation and autophagosome formation, ATG protein and lipid retrieval, fusion of the autophagosome to an lysosome/endosome and autolysosome formation, and autolysosome cargo degradation. The ULK complex, which is composed of ULK1/2, ATG13, FIP200, and ATG101, is activated by the inhibition of mTORC1 and initiates the autophagy program. The class III PI3K complex, which is composed of Beclin-1, class III PI3K (i.e., Vps34), p150 (i.e., Vps15), ATG14L, and certain regulatory factors, is essential for vesicle nucleation. Two ubiquitin-like protein conjugation systems form two important complexes (the LC3-II-PE complex and the ATG5-ATG12-ATG16L1 complex) that are critical for vesicle elongation. The transmembrane proteins VMP1 and ATG9 also play a role in nascent autophagosome formation. The major miRNAs involved in the regulation of key members of autophagy cascades are shown in the diagram in dark blue. mTORC1, mammalian target of rapamycin complex 1; ULK, UNC-51-like kinase; ATG, autophagy-related gene; FIP200, focal adhesion kinase family-interacting protein of 200 kDa; UVRAG, UV radiation resistance-associated gene; Rubicon, RUN domain protein as Beclin-1 interacting and cysteine-rich containing; PE, phosphatidylethanolamine; VMP1, vacuole membrane protein 1; PI3K, phosphatidylinositol-3 kinase. Pro-LC3, primary translation product of LC3; LC3-I, cytosolic form of LC3 that is cleaved from Pro-LC3 by ATG4; LC3-II, lipidated form of LC3 that is conjugated to PE. See the text for details.
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Figure 2: miRNAs regulate the major cascades of autophagyAutophagy includes at least six successive events: induction, vesicle nucleation (or phagophore formation), vesicle elongation and autophagosome formation, ATG protein and lipid retrieval, fusion of the autophagosome to an lysosome/endosome and autolysosome formation, and autolysosome cargo degradation. The ULK complex, which is composed of ULK1/2, ATG13, FIP200, and ATG101, is activated by the inhibition of mTORC1 and initiates the autophagy program. The class III PI3K complex, which is composed of Beclin-1, class III PI3K (i.e., Vps34), p150 (i.e., Vps15), ATG14L, and certain regulatory factors, is essential for vesicle nucleation. Two ubiquitin-like protein conjugation systems form two important complexes (the LC3-II-PE complex and the ATG5-ATG12-ATG16L1 complex) that are critical for vesicle elongation. The transmembrane proteins VMP1 and ATG9 also play a role in nascent autophagosome formation. The major miRNAs involved in the regulation of key members of autophagy cascades are shown in the diagram in dark blue. mTORC1, mammalian target of rapamycin complex 1; ULK, UNC-51-like kinase; ATG, autophagy-related gene; FIP200, focal adhesion kinase family-interacting protein of 200 kDa; UVRAG, UV radiation resistance-associated gene; Rubicon, RUN domain protein as Beclin-1 interacting and cysteine-rich containing; PE, phosphatidylethanolamine; VMP1, vacuole membrane protein 1; PI3K, phosphatidylinositol-3 kinase. Pro-LC3, primary translation product of LC3; LC3-I, cytosolic form of LC3 that is cleaved from Pro-LC3 by ATG4; LC3-II, lipidated form of LC3 that is conjugated to PE. See the text for details.
Mentions: The ULK complex, which is composed of ULK1, ULK2, ATG13, ATG101, and the focal adhesion kinase family-interacting protein of 200 kDa (FIP200), is crucial for autophagy induction. Mammalian target of rapamycin complex 1 (mTORC1) binds to and inactivates ULK1 and ULK2. The dissociation of mTORC1 from the ULK complex leads to ULK1/2 activation and the subsequent phosphorylation of FIP200 and ATG13, which initiates phagophore formation [73]. The PI3K complex, which is essential for vesicle nucleation, is composed of class III PI3K, Beclin-1, ATG14L, p150, and several regulators including Ambra1, Bif-1, UV radiation resistance-associated gene (UVRAG), Bcl-2, Bcl-xL, and the Run domain protein Rubicon [74]. The LC3 and ATG12 ubiquitin-like protein conjugation systems are responsible for vesicle elongation. In the LC3 conjugation system, ATG4 cleaves pro-LC3 into cytosolic LC3-I, which successively binds to ATG7 and ATG3. LC3-I is processed by these two autophagy-related proteins and is then coupled to phosphatidylethanolamine (PE) to become a membrane-bound PE-conjugated LC3, LC3-II. In the ATG12 conjugation system, ATG12 successively binds to ATG7, ATG10, and ATG5 and finally conjugates with autophagy-related 16-like 1 (ATG16L1) to form the ATG16L1-ATG5-AGT12 complex [74, 75]. These two ubiquitination-like systems are closely connected. For example, the ATG16L1-ATG5-AGT12 complex is localized to the phagophore and potentially acts as a novel E3-like enzyme to determine the sites at which LC3 conjugates with PE [76]. VMP1 is thought to function by recruiting Beclin-1 and other components in the class III PI3K complex to the phagophore, whereas ATG9 is thought to contribute to the delivery of membrane particles to the forming autophagosome [74]. The major autophagy cascades are depicted in Figure 2.

Bottom Line: Numerous miRNAs regulate programmed cell death including apoptosis, autophagy and necroptosis.We summarize how miRNAs regulate apoptotic, autophagic and necroptotic pathways and cancer progression.We also discuss how miRNAs link different types of cell death.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Medical School, Southeast University, Nanjing, Jiangsu 210009, China.

ABSTRACT
MicroRNAs (miRNAs) are endogenous 22 nt non-coding RNAs that target mRNAs for cleavage or translational repression. Numerous miRNAs regulate programmed cell death including apoptosis, autophagy and necroptosis. We summarize how miRNAs regulate apoptotic, autophagic and necroptotic pathways and cancer progression. We also discuss how miRNAs link different types of cell death.

No MeSH data available.


Related in: MedlinePlus