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Event: 1981

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Decreased SIRT1 expression

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Decrease,SIRT1(sirtuin 1) levels
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
DNA damage and metastatic breast cancer KeyEvent Agnes Aggy (send email) Under development: Not open for comment. Do not cite Under Development

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
human and other cells in culture human and other cells in culture Moderate NCBI
mice Mus sp. Moderate NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Adult, reproductively mature Moderate

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Female Moderate

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Biological state: 

Mammalian SIRTs include seven proteins (SIRT1-7) with deacetylase activity belonging to the class III histone deacetylase family. SIRTs share homology with the yeast deacetylase Sir2, and have different sequences and lengths in both their N- and C-terminal domains (Carafa, V. et al 2012). Expressed from bacteria to humans (Vaquero, A. 2009), SIRTs target histone and non-histone proteins.

Localization of SIRTs is restricted to mitochondria, cytoplasm and nucleus     The location of SIRT1, SIRT6, and SIRT7  is predominantly in the nucleus,  while SIRT2 in the cytosol, and SIRT3, SIRT4, and SIRT5 are in the mitochondria.  Depending on their role in regulating different pathways,  SIRTs relocalize under different conditions such as  cell cycle phase, tissue type, developmental stage, stress condition, and metabolic status which has been documented in the literature. (McGuinness, D. et al 2011).  As per Mitchishita et al, SIRT1, SIRT2, and SIRT7 are often found in both the nucleus and cytoplasm (Michishita, E et al 2005).

 Cellular pathways  like DNA repair, transcriptional regulation, metabolism, aging, and senescence are modulated by Sirtuins. This has  created  sufficient interest with Sirtuins as target in cancer research as the above mentioned functions are involved in initiation and progression of cancer. Evidence have suggested the association of SIRTs with metabolism-associated TFs, MYC and hypoxia inducible factor-1 (HIF-1),  in terms of  energy metabolic reprogramming.( Zwaans, B. M. et al 2014)

  The biological effect of SIRTs in cancer is either tumor suppression  or tumor promoter (oncogenes) action by altering the cell proliferation, differentiation, and death which in turn depends on cell context and experimental conditions.   These two totally opposite function of SIRTs on cancer cell is remains a highly debated and controversial topic. Whether SIRTs act as tumor suppressors or promoters depends on (i) their  The different expression levels of SIRTS in tumors and its effects on cell cycle, cell growth,  death, their action on specific proto-oncogene and onco-suppressor proteins will determine SIRTs role as  tumor suppressor or tumor promoters  (Deng, C. X. 2009).

Sirtuin Reactions

The NAD+-dependent deacetylation is well known enzymatic reaction catalyzed by SIRTs. Deacetylation reaction begins with amide cleavage from NAD+ with the formation of nicotinamide and an intermediate of reaction, O-ADP-ribose. This intermediate formed is necessary for the deacetylation process by which SIRTs catalyze the transfer of one acetyl group from a lysine to O-ADP-ribose moiety to form O-acetyl-ADP-ribose and the deacetylated lysine product. This reaction requires a mole equivalent of NAD+ per acetyl group removed and is controlled by the cellular [NAD]/[NADH] ratio (Sauve, A. A. 2010 and Shi, Y. et al 2013).

Among the SIRTs family, only SIRT1, SIRT2, and SIRT3 possess a robust deacetylase activity even though SIRT enzymes are primarily known as protein deacetylases. SIRT4, SIRT5, SIRT6, and SIRT7) exhibit a weak or no detectable deacetylation activity at all.Through these reactions, SIRTs are able to regulate several key cellular processes (Jiang, H., et al 2013 and Zhang, S. et al 2017).

Biological compartments: 

Regulation of gene expression takes place in the cell, subcellular site being nucleus.

General role in biology: 

Silent Inflammation Regulator 2 (SIR2) proteins belong to the  family of histone deacetylases (HDACs) that catalyze deacetylation of both histone and non- histone lysine residues.

Mammalian sirtuins (SIRT1-7) are involved in  diverse biological processes including energy metabolism,  lifespan and health span regulation (Longo VD et al 2006). Mammalian sirtuins possess will bring about an array of biological functions through its enzymatic activity such as  histone deacetylase, mono-ADP-ribosyltransferase, desuccinylase, demalonylase, demyristoylase, and depalmitoylase activity (Michan S et al 2007). SIRT1 located  in the nucleus play an important role in genomic stability, telomere maintenance, and cell survival (Chen J et al 2011 and, Haigis MC et al 2006).

Among the 7 SIRTs, SIRT1 is the largest in terms of total DNA and amino acid sequence studied sirtuin [Fang, Y. and M.B. Nicholl 2011]. SIRT1, a class 3 histone deacetylase, is implicated in the modulation of apoptosis, senescence, proliferation, and aging. It’s actions arebrought about by cellular nicotinamide adenosine dinucleotide (NAD+) which acts as a cofactor for deacetylation reactivity. The liberated nicotinamide from NAD+, generates a  novel metabolite o-acetyl-ADP-ribose . SIRT1 can mediate  the actions at translational level. Various mechanisms have been  proposed to be  involved in dysregulation of SIRT1 in cancer cells  [Yao, C., et al.2016]. In human breast, lung and prostate cancers SIRT1 is significantly elevated . It plays  a role in tumorigenesis by anti-apoptotic activity through oncogene and epigenetic regulator action.[ Saunders, L. and E. Verdin 2007]. SIRT1 deacetylates pro-apoptotic proteins such as p53 and promotes cell survival under genotoxic and oxidative stresses [Kojima, K., et al 2010]. It’s critical role in multiple aspects of resistance to anti-cancer drugs is also well documented [Duan, K., et al 2015]. Therefore, SIRT1 overexpression is associated with the subsequent higher level of tumor cell proliferation, invasion, and migration [Wang, X., et al 2016].

SIRT1 expression is increased in human colon cancer, acute myeloid leukemia, and some skin can- cers (Bradbury, C. A et al 2005, Hida, Y. et al 2007, Huffman, D. M. et al 2007 and Stunkel, W.2007). SIRT1 , by interacting with and inhibiting p53  may act as tumor promoter (van Leeuwen, I., and Lain, S. 2009). Repression of tumor suppression protein expression and DNA repair protein ,are other roles of  SIRT1 in cancer cells.  In colon cancer ,  SIRT1 limits β-catenin signaling while in breast cancer it interacts with  BRCA1 signaling . However it has been observed that  SIRT1 expression is decreased in  ovarian cancer, glioblastoma, and bladder carcinoma (Deng, C. X. 2009).  In these cancers , SIRT1 might serve as a tumor suppressor by blocking oncogenic pathways. Thus SIRT1 can serve as a tumor promoter or tumor suppressor, depending on the oncogenic pathways specific to particular tumors.

In hepatocellular carcinoma , SIRT1 was overexpressed in HCC cells and tissues, and significantly promoted the migration and invasion ability of HCC cells by inducing the epithelial and mesenchymal transition[Hao C et al 2014]. This in vivo study  also supported the oncogenic functions of SIRT1 in enhancing metastasis[Hao C et al 2014]. Bae et al [Bae HJ et al 2014] found that knockdown of SIRT1 inhibited cell growth by transcriptional deregulation of cell cycle proteins, leading to hypophosphorylation of pRb, which inactivated E2F/ DP1 target gene transcription, and thereby caused the G1/S cell cycle arrest. In addition, miR29c was identified as a suppressor of SIRT1 by comprehensive miRNA profiling and ectopic miR29c expression recapitulated SIRT1 knockdown effects in HCC cells [Bae HJ et al 2014].  To contradict the above findings,  Zhang et al [Zhang ZY et al 2015] reported that SIRT1 has anticarcinogenic effects in HCC via the AMPK mammalian target of rapamycin (mTOR) pathway. They evaluated the relationship between p53 mutations and activation of SIRT1 in 252 patients with hepatitis B virus positive HCC and found that activated SIRT1 was associated with a longer recurrence free survival in HCC tissues harbouring mutant p53.  He reported that inhibition of SIRT1 increased cell growth, bearing mutated p53, by suppressing AMPK activity and enhancing mTOR activity.The conflicting results from different published data  indicated that SIRT1 is multifunctional gene and its biological features are left unsolved.

These above evidence indicates the involvement of SIRTs in regulating three important tumor processes: epithelial-to-mesenchymal transition (EMT), invasion, and metastasis. Many SIRTs are responsible for cellular metabolic reprogramming and drug resistance by inactivating cell death pathways and promoting uncontrolled proliferation. These observations are  for the future development of novel tailored SIRT-based cancer therapies.

Wang et al showed that SIRT1 expression was increased in several cancer cell lines, and is generally associated with poor prognosis and overall survival (Wang, C., et al 2017). Vaziri et al reported that SIRT1 interacted  with P53, triggering its deacetylation in Lys382 residue, and determined a block of all P53-dependent pathways, leading to uncontrolled cell cycle and inactivation of the apoptotic process (Vaziri, H., et al 2011).

SIRT1 has a function in metastasis and invasiveness in several cancers that has been reported in several studies. Among them ,the deacetylation of many proteins involved in tumor suppressor processes or DNA damage repair, and the inactivation of specific pathways support the role of SIRT1 as a tumor promoter. The role of  SIRT1  in the initiation, promotion, and progression of several malignant tumors including prostate cancer (Jung-Hynes, B. et al 2009), breast cancer (Jin, X., et al 2018), lung cancer (Han, L. et al 2013) and gastric cancer (Han, L. et al 2013) are well documented. Wilking el al showed in his in vitro experiments that the inhibition of SIRT1 by treatment with small molecule SIRT1 inhibitors determines a significant decrease in cell growth, proliferation and viability (Wilking, M. J., et al 2014).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Method/ measurement reference


Strength of evidence

Assay fit for purpose

Repeatability/ reproducibility

Direct measure

Human tissues

qRT-PCR,Western blotting,Luciferase reporter assay H2,H4,H7,H8,H9

Micro-array (Shen ZL et al 2016)






Human cell lines

Micro-array, qRT-PCR,Western blotting,Luciferase reporter assay

(Guo S et al 2020,

Bae HJ et al 2014,

Zhou J et al 2017,

Fu H et al 2018,

Lian B et al 2018

Guan Y et al 2017

Yang X et al 2014)







qRT-PCR,Western blotting,Luciferase reporter assay,ELISA,cell culture

Bai XZ et al 2018






Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Decreased SIRT1 expression  is known to be highly conserved throughout evolution and is present from humans to invertebrates.


List of the literature that was cited for this KE description. More help

Bae, H. J., Noh, J. H., Kim, J. K., Eun, J. W., Jung, K. H., Kim, M. G., ... & Nam, S. W. (2014). MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma. Oncogene33(20), 2557-2567.

Bae, H. J., Noh, J. H., Kim, J. K., Eun, J. W., Jung, K. H., Kim, M. G., ... & Nam, S. W. (2014). MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma. Oncogene33(20), 2557-2567.

Bai, X. Z., Zhang, J. L., Liu, Y., Zhang, W., Li, X. Q., Wang, K. J., ... & Hu, D. H. (2018). MicroRNA-138 aggravates inflammatory responses of macrophages by targeting SIRT1 and regulating the NF-κB and AKT pathways. Cellular Physiology and Biochemistry49(2), 489-500.

Bradbury, C. A., Khanim, F. L., Hayden, R., Bunce, C. M., White, D. A., Drayson, M. T., ... & Turner, B. M. (2005). Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors. Leukemia19(10), 1751-1759.

Carafa, V., Nebbioso, A., & Altucci, L. (2012). Sirtuins and disease: the road ahead. Frontiers in pharmacology3, 4.

Chen, J., Zhang, B., Wong, N., Lo, A. W., To, K. F., Chan, A. W., ... & Ko, B. C. (2011). Sirtuin 1 is upregulated in a subset of hepatocellular carcinomas where it is essential for telomere maintenance and tumor cell growth. Cancer research71(12), 4138-4149..

Deng, C. X. (2009). SIRT1, is it a tumor promoter or tumor suppressor?. International journal of biological sciences5(2), 147.

Duan, K., Ge, Y. C., Zhang, X. P., Wu, S. Y., Feng, J. S., Chen, S. L., ... & Fu, C. H. (2015). miR-34a inhibits cell proliferation in prostate cancer by downregulation of SIRT1 expression. Oncology letters10(5), 3223-3227.

Fang, Y., & Nicholl, M. B. (2011). Sirtuin 1 in malignant transformation: friend or foe?. Cancer letters306(1), 10-14.

Fu, H., Song, W., Chen, X., Guo, T., Duan, B., Wang, X., ... & Zhang, C. (2018). MiRNA-200a induce cell apoptosis in renal cell carcinoma by directly targeting SIRT1. Molecular and cellular biochemistry437(1), 143-152.

Guan, Y., Rao, Z., & Chen, C. (2018). miR-30a suppresses lung cancer progression by targeting SIRT1. Oncotarget9(4), 4924.

Guo, S., Ma, B., Jiang, X., Li, X., & Jia, Y. (2020). Astragalus polysaccharides inhibits tumorigenesis and lipid metabolism through miR-138-5p/SIRT1/SREBP1 pathway in prostate cancer. Frontiers in Pharmacology11, 598.

Haigis, M. C., & Guarente, L. P. (2006). Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction. Genes & development20(21), 2913-2921.

Han, L., Liang, X. H., Chen, L. X., Bao, S. M., & Yan, Z. Q. (2013). SIRT1 is highly expressed in brain metastasis tissues of non-small cell lung cancer (NSCLC) and in positive regulation of NSCLC cell migration. International journal of clinical and experimental pathology6(11), 2357.

Hao, C., Zhu, P. X., Yang, X., Han, Z. P., Jiang, J. H., Zong, C., ... & Wei, L. X. (2014). Overexpression of SIRT1 promotes metastasis through epithelial-mesenchymal transition in hepatocellular carcinoma. BMC cancer14(1), 1-10.

Hida, Y., Kubo, Y., Murao, K., & Arase, S. (2007). Strong expression of a longevity-related protein, SIRT1, in Bowen’s disease. Archives of dermatological research299(2), 103-106.

Huffman, D. M., Grizzle, W. E., Bamman, M. M., Kim, J. S., Eltoum, I. A., Elgavish, A., & Nagy, T. R. (2007). SIRT1 is significantly elevated in mouse and human prostate cancer. Cancer research67(14), 6612-6618.

Jiang, G., Wen, L., Zheng, H., Jian, Z., & Deng, W. (2016). miR2045p targeting SIRT1 regulates hepatocellular carcinoma progression. Cell biochemistry and function34(7), 505-510.

Jiang, H., Khan, S., Wang, Y., Charron, G., He, B., Sebastian, C., ... & Lin, H. (2013). SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine. Nature496(7443), 110-113.

Jin, X., Wei, Y., Xu, F., Zhao, M., Dai, K., Shen, R., ... & Zhang, N. (2018). SIRT1 promotes formation of breast cancer through modulating Akt activity. Journal of Cancer9(11), 2012.

Jung-Hynes, B., Nihal, M., Zhong, W., & Ahmad, N. (2009). Role of sirtuin histone deacetylase SIRT1 in prostate cancer: a target for prostate cancer management via its inhibition?. Journal of Biological Chemistry284(6), 3823-3832..

Kojima, K., Fujita, Y., Nozawa, Y., Deguchi, T., & Ito, M. (2010). MiR34a attenuates paclitaxelresistance of hormonerefractory prostate cancer PC3 cells through direct and indirect mechanisms. The Prostate70(14), 1501-1512.

Lian, B., Yang, D., Liu, Y., Shi, G., Li, J., Yan, X., ... & Zhang, R. (2018). miR-128 targets the SIRT1/ROS/DR5 pathway to sensitize colorectal cancer to TRAIL-induced apoptosis. Cellular Physiology and Biochemistry49(6), 2151-2162.

Longo, V. D., & Kennedy, B. K. (2006). Sirtuins in aging and age-related disease. Cell126(2), 257-268.

Luo, J., Chen, P., Xie, W., & Wu, F. (2017). MicroRNA-138 inhibits cell proliferation in hepatocellular carcinoma by targeting Sirt1. Oncology reports38(2), 1067-1074.

McGuinness, D., McGuinness, D. H., McCaul, J. A., & Shiels, P. G. (2011). Sirtuins, bioageing, and cancer. Journal of aging research2011.

Michan, S., & Sinclair, D. (2007). Sirtuins in mammals: insights into their biological function. Biochemical Journal404(1), 1-13.

Michishita, E., Park, J. Y., Burneskis, J. M., Barrett, J. C., & Horikawa, I. (2005). Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Molecular biology of the cell16(10), 4623-4635.

Saunders, L. R., & Verdin, E. (2007). Sirtuins: critical regulators at the crossroads between cancer and aging. Oncogene26(37), 5489-5504.

Sauve, A. A. (2010). Sirtuin chemical mechanisms. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics1804(8), 1591-1603..

Shen, Z. L., Wang, B., Jiang, K. W., Ye, C. X., Cheng, C., Yan, Y. C., ... & Wang, S. (2016). Downregulation of miR-199b is associated with distant metastasis in colorectal cancer via activation of SIRT1 and inhibition of CREB/KISS1 signaling. Oncotarget7(23), 35092.

Shi, Y., Zhou, Y., Wang, S., & Zhang, Y. (2013). Sirtuin deacetylation mechanism and catalytic role of the dynamic cofactor binding loop. The journal of physical chemistry letters4(3), 491-495.

Shuang, T., Wang, M., Zhou, Y., & Shi, C. (2015). Over-expression of Sirt1 contributes to chemoresistance and indicates poor prognosis in serous epithelial ovarian cancer (EOC). Medical oncology32(12), 1-7.

Stünkel, W., Peh, B. K., Tan, Y. C., Nayagam, V. M., Wang, X., SaltoTellez, M., ... & Wood, J. (2007). Function of the SIRT1 protein deacetylase in cancer. Biotechnology Journal: Healthcare Nutrition Technology2(11), 1360-1368.

Tian, Z., Jiang, H., Liu, Y., Huang, Y., Xiong, X., Wu, H., & Dai, X. (2016). MicroRNA-133b inhibits hepatocellular carcinoma cell progression by targeting Sirt1. Experimental cell research343(2), 135-147.

van Leeuwen, I., & Lain, S. (2009). Sirtuins and p53. Advances in cancer research102, 171-195.

Vaquero, A. (2009). The conserved role of sirtuins in chromatin regulation. International Journal of Developmental Biology53(2-3), 303-322.

Vaziri, H., Dessain, S. K., Eaton, E. N., Imai, S. I., Frye, R. A., Pandita, T. K., ... & Weinberg, R. A. (2001). hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell107(2), 149-159.

Wang, C., Yang, W., Dong, F., Guo, Y., Tan, J., Ruan, S., & Huang, T. (2017). The prognostic role of Sirt1 expression in solid malignancies: a meta-analysis. Oncotarget8(39), 66343.

Wang, X., Yang, B., & Ma, B. (2016). The UCA1/miR-204/Sirt1 axis modulates docetaxel sensitivity of prostate cancer cells. Cancer chemotherapy and pharmacology78(5), 1025-1031.

Wilking, M. J., Singh, C., Nihal, M., Zhong, W., & Ahmad, N. (2014). SIRT1 deacetylase is overexpressed in human melanoma and its small molecule inhibition imparts anti-proliferative response via p53 activation. Archives of biochemistry and biophysics563, 94-100.

Yan, X., Liu, X., Wang, Z., Cheng, Q., Ji, G., Yang, H., ... & Pei, X. (2019). MicroRNA4865p functions as a tumor suppressor of proliferation and cancer stemlike cell properties by targeting Sirt1 in liver cancer. Oncology reports41(3), 1938-1948.

Yang, X., Yang, Y., Gan, R., Zhao, L., Li, W., Zhou, H., ... & Meng, Q. H. (2014). Down-regulation of mir-221 and mir-222 restrain prostate cancer cell proliferation and migration that is partly mediated by activation of SIRT1. PloS one9(6), e98833.

Yao, C., Liu, J., Wu, X., Tai, Z., Gao, Y., Zhu, Q., ... & Gao, S. (2016). Reducible self-assembling cationic polypeptide-based micelles mediate co-delivery of doxorubicin and microRNA-34a for androgen-independent prostate cancer therapy. Journal of Controlled Release232, 203-214.

Zhang S, Zhang D, Yi C, Wang Y, Wang H, Wang J. (2016). MicroRNA-22 functions as a tumor suppressor by targeting SIRT1 in renal cell carcinoma. Oncol Rep. 35(1), 559-67. 

Zhang, Z. Y., Hong, D., Nam, S. H., Kim, J. M., Paik, Y. H., Joh, J. W., ... & Kim, S. J. (2015). SIRT1 regulates oncogenesis via a mutant p53-dependent pathway in hepatocellular carcinoma. Journal of hepatology62(1), 121-130.

Zhang, S., Huang, S., Deng, C., Cao, Y., Yang, J., Chen, G., ... & Zou, X. (2017). Co-ordinated overexpression of SIRT1 and STAT3 is associated with poor survival outcome in gastric cancer patients. Oncotarget8(12), 18848.

Zhou, J., Zhou, W., Kong, F., Xiao, X., Kuang, H., & Zhu, Y. (2017). microRNA34a overexpression inhibits cell migration and invasion via regulating SIRT1 in hepatocellular carcinoma Corrigendum in/10.3892/ol. 2019.11048. Oncology letters14(6), 6950-6954.

          Zwaans, B. M., & Lombard, D. B. (2014). Interplay between sirtuins, MYC and hypoxia-inducible factor in cancer-associated metabolic reprogramming. Disease models & mechanisms7(9), 1023-1032.