TIS21 negatively regulates hepatocarcinogenesis by disruption of cyclin B1-Forkhead box M1 regulation loop

Park, Tae Jun; Kim, Ji Yeon; Oh, Seh–Hoon; Kang, So Young; Kim, Bong-Wan; Wang, Hee Jung; Song, Kye Yong; Kim, Hyoung Chin; Lim, In Kyoung

doi:10.1002/hep.22212

Cited by 71 publications

(66 citation statements)

References 61 publications

(52 reference statements)

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“…FOXM1B, the predominant FOXM1 isoform, could directly promote gastric tumorigenesis by regulating the expression of genes key to cancer biology overall [21]. Disruption of the FOXM1-cyclin B1 regulatory loop is one of the mechanisms of the negative regulation of hepatocarcinogenesis [22].…”

Section: Discussionmentioning

confidence: 99%

Expression and significance of FOXM1 in human cervical cancer: A tissue micro-array study

Guan¹,

Chen²,

Li³

et al. 2011

CIM

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Objective: is study was designed to investigate the expression and signi cance of the Forkhead Box M1 (FOXM1) transcription factor in human cervical cancer.Methods: e expression of FOXM1 protein was assessed in tissue microarrays containing 102 cervical cancer tissues by the Streptavidin-Peroxidase (SP) immunohistochemitry technique. e relationship between FOXM1 protein and clinico-pathological features (pathological stages, pathological types, TNM stage) was analyzed.Results: FOXM1 protein was located in the cytoplasma and/or nucleus. e overall expression of FOXM1 in the cytoplasm and nucleus was not associated with T stages (P=0.217) or lymph node status (P=0.313). e nuclear expression of FOXM1 protein was not associated with T stage (P=0.508) or lymph node status (P=0.345). Elevated translocation and activity of FOXM1 were discovered with a secondary analysis that showed that the di erences of the nuclear expression of FOXM1, among di erent pathological stages, were statistically signi cant (P<0.05). e nuclear expression of FOXM1 in low di erential cervical cancer tissues was signi cantly higher than in high di erential cervical cancer tissues (P<0.05).Conclusion: e overexpression of FOXM1 protein in cervical cancer maybe associated with the progression of cervical cancer, and could be a potentially novel tumor marker useful for diagnosis and therapy of cervical cancer.ORIGINAL RESEARCH

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Section: Discussionmentioning

confidence: 99%

Expression and significance of FOXM1 in human cervical cancer: A tissue micro-array study

Guan¹,

Chen²,

Li³

et al. 2011

CIM

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“…Ϫ/Ϫ MEF (24,30,31). As opposed to TIS21 ϩ/ϩ MEF, exposure of TIS21 Ϫ/Ϫ MEF to DOXO demonstrated a lower number of viable cells, suggesting the anti-apoptotic role of TIS21 gene in MEF (Fig.…”

Section: No Protective Effect Of Nac On Doxo-induced Mef Cell Death-mentioning

confidence: 92%

“…The results were expressed as A 575 obtained from 10 6 cells. Construction and Use of Adenoviral Vectors-Adenoviral vector expressing TIS21 (Ad-TIS21) was prepared as described (24). In brief, cDNA of TIS21 inserted into replication-defective E1-and E3-adenoviral vectors were transfected and then amplified in 293 human kidney epithelial cells.…”

Section: Measurement Of Intracellular Hydrogen Peroxide and Superoxidementioning

confidence: 99%

B Cell Translocation Gene 2 Enhances Susceptibility of HeLa Cells to Doxorubicin-induced Oxidative Damage

Lim

Park

Lim

2008

Journal of Biological Chemistry

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BTG2/TIS21/PC3 (B cell translocation gene 2) has been known as a p53 target gene and functions as a tumor suppressor in carcinogenesis of thymus, prostate, kidney, and liver. Although it has been known that the expression of BTG2 /TIS21/PC3 is induced during chemotherapy-mediated apoptosis in cancer cells, a role of BTG2 /TIS21/PC3 in cell death remains to be elucidated. In this study, the mechanism and role of BTG2 involved in the enhancement of doxorubicin ( TIS21(12-O-tetradecanoylphorbol-13-acetate-inducible sequence 21) was first identified as one of immediate early genes (1) in mice 3T3 fibroblasts when treated with 12-O-tetradecanoylphorbol-13-acetate (2). Since then, PC3 (pheochromocytoma cell 3) was isolated as an immediate early response gene when activated by nerve growth factor at the onset of neuronal differentiation in rat PC12 cells (3). The human homolog of TIS21, named BTG2 (B cell translocation gene 2), was cloned from a cDNA library of human lymphoblastoid cells as a gene associated with DNA damage response and contains p53 response elements in its 5Ј-flanking (Ϫ74 to Ϫ112) region (4).We previously reported that TIS21 expression was low in thymic carcinoma developed in the SV40 large T antigen transgenic mice but high in normal thymus, suggesting anticarcinogenic activity of TIS21 in thymus (5). Expressions of TIS21 in renal proximal tubule and prostate acini are lost also in the renal carcinoma and the early stage of carcinogenesis in prostate (6, 7), respectively. Consistent with these findings, Boiko et al. (8) recently ascertained BTG2 as a tumor suppressor by showing that BTG2 is a major downstream effector of p53-dependent proliferation arrest of mouse and human fibroblasts transduced with oncogenic Ras and that repression of BTG2 regulates the activities of cyclin D1 and cyclin E and phosphorylation of pRB, thus inducing neoplastic transformation of primary human fibroblasts. TIS21 has been known to work also independently of pRB and p53 in cancer cells regulating G 1 /S arrest and G 2 /M arrest by inhibiting synthesis of cyclin E and cdk4 (9), as well as interaction with cyclin B1 and the cdk1 complex (10), respectively. Moreover, persistent expression of TIS21 induces the loss of mitochondrial membrane potential differences in U937 cells (11), and transfection of TIS21 gene to Huh7 hepatoma cells significantly reduces in vivo and in vitro tumorigenesis by inhibiting feedback regulation between cyclin B1 and FoxM1 transcription factor (11), and the expression of BTG2 in human liver cancer is much lower than that of the surrounding tissues. Collectively, these findings indicate that TIS21 controls cellular process as an inhibitor of cell division cycle and a tumor suppressor, thus evading cancer development independent of p53.The level of reactive oxygen species (ROS) 2 is controlled by multiple interacting components. Among them, superoxide dismutase (SOD), glutathione peroxidase 1 (GPx), and catalase are the primary antioxidant enzymes in mammalian tissues (12,13). SOD catalyzes di...

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“…Hepatocyte-specific deficiency of the Btg2 target FoxM1b leads to impaired activity of cyclin-dependent kinase complexes involving cyclin E1, A2, and B1, but not D1, after 2/3 PH in mice (33). Moreover, Btg2 overexpression in human hepatoma cells decreases mRNA and protein levels of cyclin B1, but not cyclin D1 (34). Similarly, Pdcd4 overexpression fails to suppress cyclin D1 mRNA or protein levels (19).…”

Section: Figurementioning

confidence: 99%

A microRNA-21 surge facilitates rapid cyclin D1 translation and cell cycle progression in mouse liver regeneration

et al. 2012

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MicroRNA-21 (miR-21) is thought to be an oncomir because it promotes cancer cell proliferation, migration, and survival. miR-21 is also expressed in normal cells, but its physiological role is poorly understood. Recently, it has been found that miR-21 expression is rapidly induced in rodent hepatocytes during liver regeneration after two-thirds partial hepatectomy (2/3 PH). Here, we investigated the function of miR-21 in regenerating mouse hepatocytes by inhibiting it with an antisense oligonucleotide. To maintain normal hepatocyte viability and function, we antagonized the miR-21 surge induced by 2/3 PH while preserving baseline expression. We found that knockdown of miR-21 impaired progression of hepatocytes into S phase of the cell cycle, mainly through a decrease in levels of cyclin D1 protein, but not Ccnd1 mRNA. Mechanistically, we discovered that increased miR-21 expression facilitated cyclin D1 translation in the early phase of liver regeneration by relieving Akt1/mTOR complex 1 signaling (and thus eIF-4F-mediated translation initiation) from suppression by Rhob. Our findings reveal that miR-21 enables rapid hepatocyte proliferation during liver regeneration by accelerating cyclin D1 translation.

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TIS21 negatively regulates hepatocarcinogenesis by disruption of cyclin B1-Forkhead box M1 regulation loop

Abstract: TIS21 negatively regulated hepatocarcinogenesis in part by disruption of the FoxM1-cyclin B1 regulatory loop, thereby inhibiting proliferation of transformed cells developed in mouse and human livers.

Cited by 71 publications

References 61 publications

Expression and significance of FOXM1 in human cervical cancer: A tissue micro-array study

Expression and significance of FOXM1 in human cervical cancer: A tissue micro-array study

B Cell Translocation Gene 2 Enhances Susceptibility of HeLa Cells to Doxorubicin-induced Oxidative Damage

A microRNA-21 surge facilitates rapid cyclin D1 translation and cell cycle progression in mouse liver regeneration

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