Expression of Beclin1 in osteosarcoma and the effects of down-regulation of autophagy on the chemotherapeutic sensitivity

Zhang, Zhicai; Shao, Zengwu; Xiong, Liming; Che, Biao; Deng, Chuiwen; Xu, Weiwei

doi:10.1007/s11596-009-0613-3

Cited by 27 publications

(20 citation statements)

References 26 publications

(26 reference statements)

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“…Importantly, some of these abnormalities have been shown to correlate with clinicopathological parameters and disease outcomes including overall survival in cancer patients. These findings not only underscore a pivotal role of autophagy in tumorigenesis, but also highlight the possibility of using autophagy-associated molecules as novel prognostic markers in clinical settings (Russell et al, 1990;Eccles et al, 1992;Futreal et al, 1992;Cliby et al, 1993;Saito et al, 1993;Gao et al, 1995;Ahn et al, 2007;Miracco et al, 2007Miracco et al, , 2010Ding et al, 2008;Fujii et al, 2008;Yoshioka et al, 2008;Kim et al, 2008a;Kang et al, 2009;Lazova and Pawelek, 2009;Nomura et al, 2009;Othman et al, 2009;Pirtoli et al, 2009;Li et al, 2009Zhang et al, 2009a;Koukourakis et al, 2010;Lazova et al, 2010;Miao et al, 2010;Negri et al, 2010;Sivridis et al, 2010;Wan et al, 2010;Karpathiou et al, 2010;Chang et al, 2011;Ma et al, 2011).…”

Section: Dysregulation Of Autophagy In Human Cancersmentioning

confidence: 89%

The autophagic paradox in cancer therapy

et al. 2011

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Autophagy, hallmarked by the formation of doublemembrane bound organelles known as autophagosomes, is a lysosome-dependent pathway for protein degradation. The role of autophagy in carcinogenesis is context dependent. As a tumor-suppressing mechanism in earlystage carcinogenesis, autophagy inhibits inflammation and promotes genomic stability. Moreover, disruption of autophagy-related genes accelerates tumorigenesis in animals. However, autophagy may also act as a prosurvival mechanism to protect cancer cells from various forms of cellular stress. In cancer therapy, adaptive autophagy in cancer cells sustains tumor growth and survival in face of the toxicity of cancer therapy. To this end, inhibition of autophagy may sensitize cancer cells to chemotherapeutic agents and ionizing radiation. Nevertheless, in certain circumstances, autophagy mediates the therapeutic effects of some anticancer agents. Data from recent studies are beginning to unveil the apparently paradoxical nature of autophagy as a cellfate decision machinery. Taken together, modulation of autophagy is a novel approach for enhancing the efficacy of existing cancer therapy, but its Janus-faced nature may complicate the clinical development of autophagy modulators as anticancer therapeutics.

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Section: Dysregulation Of Autophagy In Human Cancersmentioning

confidence: 89%

The autophagic paradox in cancer therapy

et al. 2011

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“…For example, a poor prognosis in high BECLIN 1 expression patient subgroups was reported for nasopharyngeal carcinoma and osteosarcoma [31,32] . Several possible mechanisms by which autophagy promotes tumorigenicity have been suggested: autophagy may increase genomic instability [33] , increase nuclear factor κB signaling [34] , reduce senescence [35] or increase survival in oncogenic stress [36] .…”

Section: Discussionmentioning

confidence: 99%

Autophagic Markers BECLIN 1 and LC3 Are Associated with Prognosis of Multiple Myeloma

Jung¹,

Roh²,

Lee³

et al. 2015

Acta Haematol

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Background/Aims: Autophagy is crucial for the survival and function of plasma cells including protection from toxic misfolded immunoglobulin and proper energy metabolism. Multiple myeloma (MM) is an indolent but eventually fatal neoplasm of plasma cells. Autophagy may play a critical role in the survival of MM cells and their response to chemotherapeutic agents. In this study, we correlated the expression of autophagy-related proteins with the prognosis of MM. Methods: In this retrospective cohort study, we examined the expression of the autophagic markers BECLIN 1 and microtubule-associated protein light chain 3 (LC3) in 89 cases of MM biopsied from 2001 to 2004 at the Asan Medical Center. The association of the expression scores of these markers with clinical outcomes was assessed. Results: Patients with strong immunoreactivity to BECLIN 1 or LC3 had a significantly better overall survival (OS) than patients with negative to moderate immunoreactivity (p = 0.036 and 0.018, respectively). This was also true for disease-specific survival (DSS; p = 0.051 and 0.043, respectively). In addition, LC3 immunostaining remained an independent factor impacting OS (p = 0.028) and DSS (p = 0.020) after multivariate analysis. Conclusions: The results of this study suggest that higher immunoreactivity for autophagic markers in MM is associated with superior patient survival.

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“…Additionally, inhibition of autophagy could increase the chemotherapeutic sensitivity to DDP of OS (11).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-199a-5p inhibits cisplatin-induced drug resistance via inhibition of autophagy in osteosarcoma cells

Jiang

et al. 2016

Oncology Letters

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Abstract. Osteosarcoma (OS) is the most common cancer of the bone. Chemotherapy is commonly used for the clinical treatment of OS. However, chemoresistance to cisplatin [also known as diamminedichloridoplatinum (II) (DDP)] is a major obstacle for OS therapy, the underlying mechanism of which is not fully understood. The present study aimed to investigate the role of microRNA (miR)-199a-5p in the regulation of chemoresistance to DDP in OS cells. Reverse transcription-quantitative polymerase chain reaction demonstrated that the expression level of miR-199a-5p was significantly reduced in human OS MG63 cells. In addition, DDP treatment also upregulated the protein levels of light chain 3 (LC3)-II and Beclin1 as well as the ratio of LC3-II vs. LC3-I in MG63 cells, indicating that autophagy was activated. Restoration of miR-199a-5p expression promoted DDP-induced inhibition of MG63 cell proliferation and inhibited DDP-induced autophagy, as indicated by the reduced protein levels of LC3-II and Beclin1 and the ratio of LC3-II vs. LC3-I. Finally, luciferase reporter assay data revealed that miR-199a-5p directly targeted Beclin1 and negatively mediated Beclin1 expression at a post-transcriptional level in MG63 cells. In conclusion, our study suggests that miR-199a-5p promotes the cytotoxicity of DDP in OS cells via inhibition of autophagy. Therefore, miR-199a-5p/autophagy signaling is involved in chemoresistance and may become a potential target for the treatment of DDP-resistant OS.

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Expression of Beclin1 in osteosarcoma and the effects of down-regulation of autophagy on the chemotherapeutic sensitivity

Cited by 27 publications

References 26 publications

The autophagic paradox in cancer therapy

The autophagic paradox in cancer therapy

Autophagic Markers BECLIN 1 and LC3 Are Associated with Prognosis of Multiple Myeloma

MicroRNA-199a-5p inhibits cisplatin-induced drug resistance via inhibition of autophagy in osteosarcoma cells

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