p21 functions in a post-mitotic block checkpoint in the apoptotic response to vinblastine

Bene, Anca; Chambers, Timothy C.

doi:10.1016/j.bbrc.2009.01.032

Cited by 14 publications

(9 citation statements)

References 16 publications

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“…p21 is recognized to play a role in the protection of cancer cells from stress and DNA damage [ 25 ]. Our findings indicated that p21 was also a direct target of miR-106b.…”

Section: Resultsmentioning

confidence: 99%

MiR-106b induces cell radioresistance via the PTEN/PI3K/AKT pathways and p21 in colorectal cancer

et al. 2015

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BackgroundRadioresistance is a challenge in the treatment of patients with colorectal cancer (CRC). Individuals display different therapeutic responses to preoperative radiotherapy, and the need of targeted therapies is urgent. MicroRNAs (miRNAs) are involved in essential biological activities, including chemoresistance and radioresistance. Several research studies have indicated that miRNA played an important role in sensitizing cells to ionizing radiation (IR). MiR-106b, a member of the miR-106b-25 cluster, is frequently dysregulated in many human cancers, including CRC. However, the function of miR-106b in radioresistance is currently poorly understood.MethodsA series of in vitro and in vivo studies were performed to investigate the roles of miR-106b on cell radioresistance in CRC.ResultsWe found overexpression of miR-106b could induce resistance to IR in vitro and in vivo in SW620 cells. Correspondingly, knocking down miR-106b in SW480 yielded the opposite effect. In addition, overexpression of miR-106b could enhance the tumour-initiating cell capacity without or with IR condition, such as the colony sphere formation capacity and the upregulation of stemness-related genes (CD133, Sox2). We further identified PTEN and p21 as novel direct targets of miR-106b by using target prediction algorithms and a luciferase assay. Overexpression of miR-106b reduced the expression of PTEN and p21 and increased the expression of p-AKT, which is a downstream of PTEN. Restoring the expression of PTEN or p21 in stably miR-106b-overexpressed cells could rescue the effect of miR-106b on cell radioresistance. Together, the acquisition of tumour-initiating cell capacity endowed CRC cells with the potential of resistance to irradiation.ConclusionsThese observations illustrated that miR-106b could induce cell radioresistance by directly targeting PTEN and p21, this process was accompanied by tumour-initiating cell capacity enhancement, which is universally confirmed to be associated with radioresistance. Our data suggested that miR-106b at least partly induces cell radioresistance in CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0592-z) contains supplementary material, which is available to authorized users.

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“…p21 is recognized to play a role in the protection of cancer cells from stress and DNA damage [ 25 ]. Our findings indicated that p21 was also a direct target of miR-106b.…”

Section: Resultsmentioning

confidence: 99%

MiR-106b induces cell radioresistance via the PTEN/PI3K/AKT pathways and p21 in colorectal cancer

et al. 2015

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“…However, p21 has also been linked to maintenance of self-renewal capacity in leukemic and normal hematopoietic stem cells, indicating that cellular context can impact on functional properties of these regulators (Cheng et al, 2000;Viale et al, 2009). Although, to our knowledge, there are no reports on a role for p21 in CC-IC self-renewal, p21 has a well-established role in protecting colon cancer cells against a variety of stress stimuli, including exposure to radiation and chemotherapy (Mahyar-Roemer and Roemer, 2001;Bene and Chambers, 2009;Gorospe et al, 1996;Sharma et al, 2005;Tian et al, 2000). These studies point to the plausibility that therapy resistance may be linked to tumor initiation and maintenance mechanisms and that pathways driving self-renewal may also function to protect CC-ICs when exposed to environmental stress.…”

Section: Significancementioning

confidence: 99%

ID1 and ID3 Regulate the Self-Renewal Capacity of Human Colon Cancer-Initiating Cells through p21

et al. 2012

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There is increasing evidence that some cancers are hierarchically organized, sustained by a relatively rare population of cancer-initiating cells (C-ICs). Although the capacity to initiate tumors upon serial transplantation is a hallmark of all C-ICs, little is known about the genes that control this process. Here, we establish that ID1 and ID3 function together to govern colon cancer-initiating cell (CC-IC) self-renewal through cell-cycle restriction driven by the cell-cycle inhibitor p21. Regulation of p21 by ID1 and ID3 is a central mechanism preventing the accumulation of excess DNA damage and subsequent functional exhaustion of CC-ICs. Additionally, silencing of ID1 and ID3 increases sensitivity of CC-ICs to the chemotherapeutic agent oxaliplatin, linking tumor initiation function with chemotherapy resistance.

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“…Mechanisms of apoptosis and their effector proteins included pro-apoptotic protein, anti-apoptotic Bcl-2 family members, and inhibitor of apoptosis proteins (IAP) [26]. BIM, Caspase3, HSP60, p21 and p53 were all pro-apoptotic proteins, which may contribute to apoptosis induction [27][28][29][30]. Caspase3 functions as an executor of apoptosis by activating DNA fragmentation [31].…”

Section: Discussionmentioning

confidence: 99%

GSG2 knockdown suppresses cholangiocarcinoma progression by regulating cell proliferation, apoptosis and migration

Zhou¹,

Huang

Nie

et al. 2020

Preprint

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Background: Cholangiocarcinoma (CCA) is the second most common type of hepatocellular carcinoma with high aggressiveness and extremely poor prognosis. Homo sapiens germ cell associated 2 (GSG2) is a histone H3 threonine-3 kinase required for normal mitosis. Nevertheless, the role and mechanism of GSG2 in progression and development of CCA remain elusive. Methods: In the present study, correlation between GSG2 and CCA was elaborated by IHC, Mann-Whitney U and Spearman grading correlation. GSG2 knockdown cell lines were successfully constructed and further used to construct mouse xenotransplantation models. Subsequently, cell proliferation, cell apoptosis, cell cycle and cell migration were detected by MTT assay, Flow Cytometry and wound-healing assay, respectively. Results: It was demonstrated that GSG2 was overexpressed in CCA specimens and relevant cell lines. The statistical analysis determined that high GSG2 expression was positively associated with more advanced tumor grade. Importantly, GSG2 knockdown inhibited cell proliferation, migration, promoted cell apoptosis and arrested cell cycle in G2 phase. Meanwhile, in vivo results also supported that GSG2 knockdown inhibit tumor growth. Additionally, GSG2 was involved in CCA progression via suppressing EMT. Conclusions: In summary, our findings suggested that GSG2 may be a potential therapeutic target for CCA patients.

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p21 functions in a post-mitotic block checkpoint in the apoptotic response to vinblastine

Cited by 14 publications

References 16 publications

MiR-106b induces cell radioresistance via the PTEN/PI3K/AKT pathways and p21 in colorectal cancer

MiR-106b induces cell radioresistance via the PTEN/PI3K/AKT pathways and p21 in colorectal cancer

ID1 and ID3 Regulate the Self-Renewal Capacity of Human Colon Cancer-Initiating Cells through p21

GSG2 knockdown suppresses cholangiocarcinoma progression by regulating cell proliferation, apoptosis and migration

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