Review Article

Epigenetic Control of Autophagy by MicroRNAs in Ovarian Cancer

Table 1

(a) Autophagy-related genes and their function identified as targets of the microRNA involved in ovarian cancer development and progression (miRanda release, August 2010; TargetScan release 6.2.). (b) Genes coding for autophagy-regulating molecules identified as targets of the microRNA involved in ovarian cancer development and progression (miRanda release, August 2010; TargetScan release 6.2.).
(a)

miRNAs (involved in ovarian cancer progression)Predicted autophagy
Target Genes
FunctionTarget prediction
miRandaTargetScan

hsa-miR-141
hsa-miR 200a
ATG7 A ubiquitin-activating (E1) enzyme homolog that activates both ATG8/LC3 and ATG12YesYes

hsa-miR-199a -5pATG14L A component of the class III PtdIns 3-kinase complexNoYes
ATG4D Processing of MAP1-LC3YesYes
BECN1 BCL-2 interacting myosin/moesin-like coiled-coil protein 1, part of the class III PtdIns 3-kinase complex (activating macroautophagy)YesYes

hsa-miR-214ATG14L A component of the class III PtdIns 3-kinase complexNoYes

hsa-miR-182ATG7 A ubiquitin-activating (E1) enzyme homolog that activates both ATG8/LC3 and ATG12YesYes
ATG16L1 A component of the ATG12-ATG5-ATG16 complex for the formation of autophagosomeYesYes
MAP1LC3B Microtubule-associated protein 1 light chain 3, precursor of LC3-II inserted in autophagosomal membranesYesYes

hsa-miR-140-5pATG14L A component of the class III PtdIns 3-kinase complexNoYes

hsa-miR-125bUVRAG Interacting with Beclin-1 and Bif-1 (activation and stimulation of macroautophagy)YesYes

hsa-miR-34aATG4B Processing of MAP1-LC3YesYes
ATG9A A transmembrane protein involved in lipid transport for phagophore expansionYesYes

hsa-let-7aATG4B Processing of MAP1-LC3YesYes
ATG9A A transmembrane protein involved in lipid transport for phagophore expansionYesYes
ATG16L1 A component of the ATG12-ATG5-ATG16 complex for the formation of autophagosomeYesYes

hsa-miR-15a
hsa-miR-15b
ATG13 A component of the ULK1 complex needed for ULK1 kinase activityNoYes
ATG9A A transmembrane protein involved in lipid transport for phagophore expansionYesYes
ATG14L A component of the class III PtdIns 3-kinase complexNoYes

hsa-miR-210ATG7 A ubiquitin-activating (E1) enzyme homolog that activates both ATG8/LC3 and ATG12YesYes

hsa-miR-449bATG4B Processing of MAP1-LC3YesYes

(b)

miRNAs (involved in
ovarian cancer progression)
Predicted autophagy
Target genes
FunctionTarget prediction
miRandaTargetScan

hsa-miR-141
hsa-miR 200a
PTEN Protein/lipid phosphatase that reduces the level of PIP3, thus limiting the activation of AKTYesYes
TSC1 Tuberose Sclerosis Complex component that negatively regulates mTORYesYes

hsa-miR 200b
hsa-miR 200c
PTEN Protein/lipid phosphatase that reduces the level of PIP3, thus limiting the activation of AKTYesYes

hsa-miR 21TSC1 Tuberose Sclerosis Complex component that negatively regulates mTORYesYes
BCL2 Interactor of Beclin-1 (represses autophagy) and of BAX (represses apoptosis)YesYes

hsa-miR-125bUVRAG Interacting with Beclin-1 and Bif-1 (activation and stimulation macroautophagy)YesYes
BCL2 Interactor of Beclin-1 (represses autophagy) and of BAX (represses apoptosis)YesYes

hsa-miR-101MTOR Mammalian target of rapamycin (kinase) component of MTORC1 (that inhibits autophagy) and of MTORC2 (that phosphorylates Akt)NoYes
RAB5A Endocytic vesicle associated ras-homolog GTPase (involved in autophagosome formation)YesYes

hsa-miR-31RAB1B Endocytic vesicle associated ras-homolog GTPase
(involved in autophagosome formation)
Yes Yes

hsa-miR-34aBCL2 Interactor of Beclin-1 (represses autophagy) and of BAX (represses apoptosis)YesYes

has-let-7aTSC1 Tuberose Sclerosis Complex component that negatively regulates mTORYes Yes

hsa-miR-15a
hsa-miR-15b
BCL2 Interactor of BECLIN 1 (represses autophagy) and of BAX (represses apoptosis)Yes Yes
TSC1 Tuberose Sclerosis Complex component that negatively regulates mTORYes Yes
FKBP1A An immunophilin that forms a complex with rapamycin and inhibits mTOR activityYes Yes

hsa-miR-155PDK1 Kinase that phosphorylates AKT in Thr308Yes Yes
RPTOR Regulatory associated protein of mTOR (component of MTORC1)No Yes

hsa-miR-99a
hsa-miR-100
MTOR Mammalian target of rapamycin (kinase) component of MTORC1 (that inhibits autophagy) and of MTORC2 (that phosphorylates Akt)No Yes

hsa-miR-449bBCL2 Interactor of Beclin-1 (represses autophagy) and of BAX (represses apoptosis)Yes Yes