Upregulation of the Kank1 gene-induced brain glioma apoptosis and blockade of the cell cycle in G0/G1 phase

Guo, Xutao; Fan, Wenhai; Bian, Xinchao; Ma, Dihui

doi:10.3892/ijo.2014.2247

Cited by 17 publications

(19 citation statements)

References 31 publications

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“…Similarly, a recent study with glioma cell lines confirmed that KANK1 transient re-expression was able to block cells in the G 1 /G 0 phase32. Although cell growth suppression is consistent with previous reports, G 1 /G 0 cell cycle arrest was not seen in our doxycycline-inducible stable MPNST cells.…”

Section: Discussionsupporting

confidence: 93%

KANK1 inhibits cell growth by inducing apoptosis through regulating CXXC5 in human malignant peripheral nerve sheath tumors

Cui

Shen

Chen

et al. 2017

Sci Rep

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Malignant peripheral nerve sheath tumors (MPNSTs) are a type of rare sarcomas with a poor prognosis due to its highly invasive nature and limited treatment options. Currently there is no targeted-cancer therapy for this type of malignancy. Thus, it is important to identify more cancer driver genes that may serve as targets of cancer therapy. Through comparative oncogenomics, we have found that KANK1 was a candidate tumor suppressor gene (TSG) for human MPNSTs. Although KANK1 is known as a cytoskeleton regulator, its tumorigenic function in MPNSTs remains largely unknown. In this study, we report that restoration of KANK1 in human MPNST cells inhibits cell growth both in human cell culture and xenograft mice by increasing apoptosis. Consistently, knockdown of KANK1 in neurofibroma cells promoted cell growth. Using RNA-seq analysis, we identified CXXC5 and other apoptosis-related genes, and demonstrated that CXXC5 is regulated by KANK1. Knockdown of CXXC5 was found to diminish KANK1-induced apoptosis in MPNST cells. Thus, KANK1 inhibits MPNST cell growth though CXXC5 mediated apoptosis. Our results suggest that KANK1 may function as a tumor suppressor in human MPNSTs, and thus it may be useful for targeted therapy.

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Section: Discussionsupporting

confidence: 93%

KANK1 inhibits cell growth by inducing apoptosis through regulating CXXC5 in human malignant peripheral nerve sheath tumors

Cui

Shen

Chen

et al. 2017

Sci Rep

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“…High grade glioma is the leading cause of brain cancer-related mortality due to its high invasive ability and malignant proliferation (1,2). Glioma incidence accounts for approximately 40-50% of all intracranial tumors (3).…”

Section: Introductionmentioning

confidence: 99%

Dracorhodin perchlorate induces the apoptosis of glioma cells

et al. 2016

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Abstract. Dracorhodin perchlorate (Dp), a synthetic analogue of the antimicrobial anthocyanin red pigment, has recently been shown to induce apoptotic cell death in various types of cancer cells. Yet, the inhibitory effect of Dp on human glioma cells remains uninvestigated. Therefore, in the present study, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to detect cell viability and cell cycle progression in glioma U87MG and T98G cells, respectively. Annexin V-FITC/propidium iodide double staining and JC-1 staining were separately applied to determine cellular apoptosis and mitochondrial membrane potential damage in the cells. The expression levels of associated proteins involved in cell cycle progression and apoptosis were measured by western blotting. The activities of caspase-9/-3 were determined by Caspase-Glo-9/3 assay. The results indicated that Dp treatment significantly inhibited cell proliferation in a dose-and time-dependent manner, and blocked cell cycle progression at the G 1 /S phase in the U87MG and T98G cells via the upregulation of p53 and p21 protein expression, and simultaneous downregulation of Cdc25A, Cdc2 and P-Cdc2 protein expression. Additionally, Dp treatment led to the loss of cellular mitochondrial membrane potential, and the release of cytochrome c, and strongly induced the occurence of apoptosis. Increased expression levels of Bim and Bax protein and the downregulated expression of Bcl-2 protein were observed. Caspase-9/-3 were activated and their activities were elevated after Dp treatment. These findings indicate that Dp inhibits cell proliferation, induces cell cycle arrest and apoptosis in glioma cells, and is a possible candidate for glioma treatment. IntroductionBrain glioma is the most common form of neural malignancy in the nervous system. High grade glioma is the leading cause of brain cancer-related mortality due to its high invasive ability and malignant proliferation (1,2). Glioma incidence accounts for approximately 40-50% of all intracranial tumors (3). Although current treatment has modestly improved patient survival, patients with gliomas still have a very poor prognosis and low cure rates. It was reported that patients with anaplastic astrocytoma have a median survival of 2-3 years, but for those with more aggressive glioblastomas, the median survival is only 12-15 months (4,5). Currently, surgery is considered as an important initial clinical approach for glioma, yet it is difficult to completely remove diffuse tumor cells. Radiotherapy and chemotherapy after initial surgical resection are regarded as an effective therapeutic plan to prevent disease recurrence (6). However, most attempts to increase the efficacy of radiotherapy and chemotherapy are hampered by unacceptable late toxicities (7). In addition, the drug-resistance of tumor cells finally results in the abrogation of the effects of current chemotherapeutic agents (8). Accordingly, to improve the prognosis and quality of life of patients with gliomas, the ...

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“…Therefore, we detected Bcl ¡ 2 and its related BAX, Caspase-9 and Caspase-3 expression, 20 and found that Bcl ¡ 2 levels increased, whereas BAX levels decreased in irradiationinduced A549/34R cells compared with those in A549 controls (Fig. 3C).…”

Section: 19mentioning

confidence: 99%

MiR-320a effectively suppresses lung adenocarcinoma cell proliferation and metastasis by regulating STAT3 signals

et al. 2017

Cancer Biology & Therapy

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MicroRNAs play important roles in tumorigenesis of various types of cancers. MiR-320a can inhibits cell proliferation of some cancers, but the biologic roles of miR-320a in lung cancer need to be further studied. Here, we investigated the roles of miR-320a in suppressing the proliferation of lung adenocarcinoma cells. MiR-320a treatment was found to effectively suppress LTEP-a-2 and A549 cell proliferation, and induce more apoptotic cells with irradiation treatment compared with control treatment. Our results also showed that miR-320a, as a novel miRNA, directly regulated signal transducer and activator of transcription 3 (STAT3) and its signals, such as Bcl ¡ 2, Bax, and Caspase 3. The siRNA-inhibited STAT3 levels further proved its roles in regulating STAT3 signals. Moreover, miR-320a treatment effectively suppressed cancer cell growth in mice xenografts compared with controls, and significantly inhibited cell migration in vitro and in vivo. Our findings collectively demonstrated that miR-320a, by directly regulating STAT3 signals, not only suppressed cell proliferation and metastasis, but also enhanced irradiation-induced apoptosis of adenocarcinomia cells.Abbreviations: GFP, green fluorescent protein; HE, hematoxylin-eosin staining; miRNAs, microRNAs; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NSCLC, Non-small cell lung cancer; STAT3, signal transducer and activator of transcription 3

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Upregulation of the Kank1 gene-induced brain glioma apoptosis and blockade of the cell cycle in G0/G1 phase

Cited by 17 publications

References 31 publications

KANK1 inhibits cell growth by inducing apoptosis through regulating CXXC5 in human malignant peripheral nerve sheath tumors

KANK1 inhibits cell growth by inducing apoptosis through regulating CXXC5 in human malignant peripheral nerve sheath tumors

Dracorhodin perchlorate induces the apoptosis of glioma cells

MiR-320a effectively suppresses lung adenocarcinoma cell proliferation and metastasis by regulating STAT3 signals

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