Orchestrating Cellular Balance: ncRNAs and RNA Interactions at the Dominant of Autophagy Regulation in Cancer
Abstract
:1. Introduction
2. Autophagy-Related Genes and Cancer
3. Regulation Roles of ncRNAs in Autophagy
3.1. Regulation of ncRNAs in Autophagy Initiation
3.2. Regulation of ncRNAs in Vesicle Nucleation
3.3. Regulation of ncRNAs in Autophagic Vesicle Elongation
3.4. Regulation of ncRNAs in Autophagosome Formation and Maturation
4. Conclusions and Perspective
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Autophagy Stage | Name | Composition |
---|---|---|
Initiation | Energy depletion | AMPK |
mTOR complex | mTORC1 | |
mTORC2 | ||
Class III PI3K complex | Vps34 | |
Vps15 | ||
ULK complexes | FIP200 | |
ULK1 | ||
ULK2 | ||
ATG13 | ||
ATG101 | ||
Class II PI3K complex | Beclin-1 | |
Vesicle nucleation | Class III PI3K complex | Vps34 |
Vps15 | ||
Class II PI3K complex | Beclin-1 | |
Bcl-2 family | Bcl-2 | |
- | ATG14 | |
Vesicle elongation | Atg12-Atg5-Atg16 | ATG7 |
ATG5 | ||
ATG12 | ||
ATG16 | ||
LC3 | LC3-I | |
LC3-II | ||
ATG4B | ||
Autophagosome formation (Vesicle fusion) | STX17 | |
- | ATG10 | |
LC3 | LC3-I | |
LC3-II | ||
- | Rab7 | |
- | Rab5 | |
- | Rab9 | |
Maturation and degradation | - | p62 |
LC3 | LC3II | |
- | Rab7 | |
- | Rab8B | |
- | Rab24 | |
LAMP | LAMP1 | |
LAMP2 | ||
LAMP3 |
Autophagy Stage | miRNA | Disease/Cancer | Target | Function | Signaling Pathway/Axis | Ref. |
---|---|---|---|---|---|---|
initiation | miR-20a/20b | breast cancer | RB1CC1/FIP200 | Overexpression of miR-20a and miR-20b attenuates autophagy | - | [44] |
initiation | miR-106a | lung adenocarcinoma | ULK1 | miRNA-106a targeted ULK1 results in death of different NSCLC cells | miR-106a-ULK1 | [45] |
initiation | miR-489 | breast cancer | ULK1, LAPTM4B | miR-489 affects autophagy by targeting ULK1 | - | [46] |
initiation | miR-25 | breast cancer | ULK1 | miR-25 functions as a regulator of autophagy by targeting ULK1 | - | [47] |
initiation | miR-142-5p | gastric cancer | ULK1 | miR-142-5p can regulate ULK1 expression | - | [48] |
initiation | miR-26 | non-small cell lung cancer | TGF-β1 | miR-26 reduces autophagy via targeting TGF-β1 | TGF-β1-JNK | |
initiation | miR-17-5p | cells | ULK1 | miR-17-5p inhibits ULK1 expression in cellular autophagy | - | [49] |
initiation | miR-26b | breast cancer | DRAM1 | miR-26b can suppress autophagy in breast cancer cells | TGF-β1-JNK | [50] |
initiation | miR-885-3p | squamous cell carcinoma | ULK2 | miR-885-3p contributes to the regulation of squamous cell carcinoma cell autophagy | - | [51] |
initiation | miR-133a-3p | gastric cancer | ATG13, GABARAPL1 | miR-133a-3p expression inhibits autophagy to hinder gastric cancer metastasis via blocking GABARAPL1 and ATG13 expression | - | [52] |
initiation | miR-20a | C2C12 myoblasts | ULK1 | miR-20a inhibits the expression of ULK1, which leads to a reduction in autophagy induced by leucine deprivation | PI3K-AKT- MTOR | [53] |
initiation | miR-100 | renal cell carcinoma | mTOR | miR-100 can inactivate mTOR and thus increase autophagy in renal cancer cells. | mTOR | [54] |
vesicle nucleation | miR-30a | hepatic fibrosis | Beclin-1 | Overexpression of miR-30a inhibits Beclin1-mediated autophagy to prevent the occurrence of liver fibrosis | - | [55] |
vesicle nucleation | miR-93 | glioblastoma | BECN1, Beclin-1, ATG5, ATG4B, SQSTM1/p62 | miR-93 inhibits autophagy functions by targeting multiple autophagy regulators | PI3K-AKT | [56] |
vesicle nucleation | miR-124-3p | breast cancer | Beclin-1, LC3-I | miR-124-3p promotes the progression of breast cancer cells by enhancing the expression of Beclin-1 | - | [57] |
vesicle nucleation | miR-30a | cardiomyocyte | Beclin-1 | Downregulation of miR-30a expression upregulates beclin-1 expression and enhances autophagy in cardiomyocytes | - | [58] |
vesicle nucleation | miR-30a | medulloblastoma | Beclin-1, LC3B | miR-30a inhibits autophagy by downregulating the expression of Beclin-1and LC3B | - | [59] |
vesicle nucleation | miR-30e | cardiomyopathy | Beclin-1, LC3-I, LC3-II | miR-30e can downregulate the expression of Beclin-1 | - | [60] |
vesicle nucleation | miR-30d | colon cancer | Beclin-1 | Overexpression of miR-30d inhibits the proliferation of colon cancer cells | - | [61] |
vesicle nucleation | miR-30d | renal cell carcinoma | MTDH | miR-30d targets MTDH and inhibits renal cancer cells | AKT/FOXO | [62] |
vesicle nucleation | miR-124-3p | breast cancer | Beclin-1 | Decreased miR-124-3p expression prompts breast cancer cell progression | - | [57] |
vesicle nucleation | miR-216b | non-small cell lung cancer | Beclin-1 | miR-216b can inhibit cisplatin sensitivity of NSCLC through regulating apoptosis and autophagy via miR-216b/Beclin-1 pathway | miR-216b/Beclin-1 axis | [63] |
vesicle nucleation | miR-17-5p | non-small cell lung cancer | Beclin-1 | miR-17-5p facilitates the ability of cell proliferation, inhibits autophagy and apoptosis by modulating Beclin-1 | - | [64] |
vesicle nucleation | miR-143 | colorectal cancer | Beclin-1 | miR-143 targets various cellular that are involved in the autophagy pathways pathogenesis of colorectal cancer | PI3K/AKT/Wnt | [65] |
elongation | miR-23a | fibroblasts | AMBRA1 | miR-23a inhibits the autophagy of fibroblasts during UV-induced photoaging | - | [66] |
elongation | miR-23a-5p | acute myeloid leukemia | TLR2 | Downregulation of miR-23a-5p in leukemic cells can lead to the upregulation of protective autophagy | - | [67] |
elongation | miR-7 | lung cancer | AMBRA1 | AMBRA1 is targeted by miR-7, leading to the promotion of lung cancer cell proliferation | AKT | [68] |
elongation | miR-128a | osteoarthritis | ATG12 | ATG12, induced by miR-128a, loss represses chondrocyte autophagy to aggravate OA progression | - | [69] |
elongation | miR-23b | traumatic brain injury | ATG12 | miR-23b directly targets to the 3′UTR region of ATG12 to suppress the activation of neuronal autophagy | - | [70] |
elongation | miR-214 | colorectal cancer | ATG12, LC3 | miR-214 inhibits autophagy and induction of apoptosis by targeting ATG12 | - | [71] |
autophagosome formation | miR-106b | colorectal cancer | ATG16L1 | miR-106b inhibits starvation-induced autophagy by inhibiting the expression of ATG16L1 | - | [72] |
autophagosome maturation | miR-138-5p | pancreatic cancer | SIRT1 | miR-138-5p specifically targets SIRT1, thereby inhibiting autophagy. | - | [73] |
autophagosome maturation | miR-487b-5p | lung cancer | LAMP2 | miR-487b-5p directly targets LAMP2 to affect the latter stage of autophagy flux in lung cancer | - | [74] |
autophagosome maturation | miR-205 | prostate cancer | RAB27A, LAMP3 | miR-205 inhibits autophagy in prostate cancer cells | - | [75] |
autophagosome maturation | miR-378 | - | PDK1 | miR-378 promotes autophagy initiation through the mammalian target of rapamycin mTOR/ULK1 pathway and sustains autophagy by targeting phosphoinositide-dependent protein kinase 1 (PDK1) | mTOR/ULK1 | [76] |
Autophagy Stage | lncRNA | Cancer/Disease | Target | Function | Signaling Pathways/Axis | Refs. |
---|---|---|---|---|---|---|
initiation | lncRNA NBR2 | colorectal cancer | AMPK | AMPK promotes the activation of autophagy by binding to lncRNA NBR2 | mTOR | [77] |
initiation | lncRNA AD5-A lncRNA | hepatocellular carcinoma (HCC) | AKT, mTOR | Overexpression of AD5-A lncRNA can block the function of miRNAs to inhibit AKT/mTOR activity and promote autophagy activation | AKT/mTOR | [78] |
initiation | lncRNA SNHG6 | colorectal cancer | ULK1 | lncRNA SNHG6 is able to promote colorectal cancer chemoresistance and enhance autophagy through regulation of ULK1 | - | [79] |
initiation | lncRNA MALAT1 | brain microvascular endothelial cell injury | ULK2 | lncRNA MALAT1 can promote the expression of ULK2, suggesting that MALAT1 protects brain microvascular endothelial cells from ischemia-reperfusion injury by promoting autophagy | - | [80] |
initiation | lncRNA H19 | cardiomyocytes | DIRAS3 | H19 could inhibit cardiomyocyte autophagy by epigenetically silencing DIRAS3 | mTOR | [81] |
initiation | lncRNA SNHG1 | parkinson’s disease | LC3-II | Downregulated lncRNA SNHG1 inhibits the mTOR pathway and initiates autophagy | mTOR | [82] |
initiation | lncRNA AK156230 | mouse embryonic fibroblasts | mTOR | AK156230 can inhibit replicative senescence (RS); meanwhile, the mTOR signaling pathway leads to autophagy deficiency, which may accelerate aging | mTOR | [83] |
initiation | lncRNA PTENP1 | hepatocellular carcinoma cells | AKT | Overexpression of lncRNA PTENP1 indirectly inhibits the PI3K/AKT pathway and then induces pro-death autophagy, leading to the death of hepatocellular carcinoma cells | PI3K/AKT | [84,85] |
vesicle nucleation | lncRNA SNHG12 | SH-SY5Y cells | LC3-II, Beclin-1 | The expression of lncRNA SNHG12 promotes LC3-II and Beclin-1 expression levels, thus inducing autophagy activation | - | [86] |
vesicle nucleation | lncRNA AC023115.3 | human glioblastoma cells | Beclin-1 | AC023115.3 is induced by cisplatin, and elevated AC023115.3 promotes cisplatin-induced apoptosis by inhibiting autophagy | miR-26a-GSK3β-Mcl1 axis | [87] |
vesicle nucleation | lncRNA PVT1 | - | ATG14 | PVT1 interacts with ATG14 in the cytoplasm, and PVT1 can upregulate the expression of both Pygo2 and ATG14, thus regulating autophagic activity | - | [88] |
vesicle nucleation | lncRNA EIF3J-DT | gastric cancer | ATG14 | EIF3J-DT activates autophagy and induces drug resistance in gastric cancer cells by targeting ATG14, thus contributing to activation of autophagy | - | [89] |
vesicle nucleation | lncRNA NEAT1 | Parkinson’s disease | LC3-II | lncRNA NEAT1 can induce abnormal autophagy by stabilizing PINK1, which is an LC3-II upstream regulatory factor and plays a role in the pathogenesis of PD | - | [90] |
elongation | lncRNA CCAT1 | hepatocellular carcinoma cell | ATG7 | lncRNA CCAT1 facilitates hepatocellular carcinoma cell autophagy and cell proliferation, and then regulates ATG7 expression | - | [91] |
elongation | lncRNA GAS5 | osteoarthritis | Beclin-1, ATG3, ATG5, ATG7, ATG12 | lncRNA GAS5, upregulating in osteoarthritis (OA), contributes to the pathogenesis of OA and thereby represses autophagy | - | [92] |
elongation | lncRNA HNF1A-AS1 | hepatocellular carcinoma | ATG5, Beclin-1, ATG12 | lncRNA HNF1A-AS1, binding to its target Beclin-1, ATG5, and ATG12, can provoke autophagy in hepatocellular carcinoma | - | [93] |
elongation | lncRNA HOTAIR | hepatocellular carcinoma | ATG3, ATG7 | lncRNA HOTAIR is upregulated to promote hepatocellular carcinoma cell proliferation, probably by enhancing ATG3 and ATG7 expression | - | [94] |
elongation | lncRNA HULC | epithelial ovarian carcinoma | ATG7, LC3-II, LAMP1 | lncRNA HULC overexpression reduces ATG7, LC3-II, and LAMP1 expression, and then reduces apoptosis and inhibits autophagy | - | [95] |
Autophagy Stage | circRNA | Cancer/Disease | Target | Function | Signaling Pathway/Axis | Ref. |
---|---|---|---|---|---|---|
initiation | circ_0009910 | chronic myeloid leukemia | ULK1 | circ_0009910 can regulate the expression of ULK1, thereby activating the level of autophagy | - | [96] |
initiation | circ_CDYL | breast cancer | ATG7, ULK1 | circ_CDYL regulates the expression of autophagy-related genes ATG7 and ULK1, thus promoting autophagy | - | [97] |
initiation | circ_PAN3 | acute myeloid leukemia | mTOR | circ-PAN3 regulates autophagy via the AMPK/mTOR signaling pathway in acute myeloid leukemia | AMPK/mTOR | [98] |
initiation | circRNA ACR | RSC96 cells | mTOR | circRNA ACR in RSC96 cells promotes the activation of the PI3K/AKT/mTOR pathway to alleviate autophagy | PI3K/AKT/mTOR | [99] |
initiation | circRNA ciRS-7 | esophageal squamous cell carcinoma | mTOR | circRNA ciRS-7 affects the AKT–mTOR signaling pathway, thus inhibiting autophagy of ESCC cells | AKT-mTOR | [100] |
vesicle nucleation | circ_MUC16 | epithelial ovarian cancer | Beclin1, RUNX1, ATG13 | circ_MUC16 promotes autophagy in epithelial ovarian cancer by regulating Beclin1, RUNX1, and ATG13 | - | [101] |
vesicle nucleation | circPOFUT1 | gastric cancer | ATG12 | circPOFUT1 promotes ATG12 expression to regulate autophagy-associated chemoresistance in gastric cancer | - | [102] |
elongation | circ_0092276 | breast cancer | ATG7, LC3-II, LC3-I, Beclin-1 | circ_0092276 affects autophagy and proliferation, and represses apoptosis of breast cancer cells | - | [103] |
elongation | circ_0035483 | renal clear cell carcinoma cells | LC3-II, LC3-I | when circ_0035483 expression is downregulated, the LC3II/LC3I ratio is significantly reduced, thus inhibiting autophagy | - | [104] |
Autophagosome formation | circ_ PABPN1 | intestinal epithelial cells | ATG16L1 | circ_ PABPN1 inhibits ATG16L1 translation and thus regulates autophagy in intestinal epithelial cells | - | [105] |
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Yang, X.; Xiong, S.; Zhao, X.; Jin, J.; Yang, X.; Du, Y.; Zhao, L.; He, Z.; Gong, C.; Guo, L.; et al. Orchestrating Cellular Balance: ncRNAs and RNA Interactions at the Dominant of Autophagy Regulation in Cancer. Int. J. Mol. Sci. 2024, 25, 1561. https://doi.org/10.3390/ijms25031561
Yang X, Xiong S, Zhao X, Jin J, Yang X, Du Y, Zhao L, He Z, Gong C, Guo L, et al. Orchestrating Cellular Balance: ncRNAs and RNA Interactions at the Dominant of Autophagy Regulation in Cancer. International Journal of Molecular Sciences. 2024; 25(3):1561. https://doi.org/10.3390/ijms25031561
Chicago/Turabian StyleYang, Xueni, Shizheng Xiong, Xinmiao Zhao, Jiaming Jin, Xinbing Yang, Yajing Du, Linjie Zhao, Zhiheng He, Chengjun Gong, Li Guo, and et al. 2024. "Orchestrating Cellular Balance: ncRNAs and RNA Interactions at the Dominant of Autophagy Regulation in Cancer" International Journal of Molecular Sciences 25, no. 3: 1561. https://doi.org/10.3390/ijms25031561