Analysis of Survivin Expression in the Subtypes of Lymphoma

Gu, Xia; Lin, Haoran

doi:10.1007/s10330-004-0351-8

Cited by 8 publications

(6 citation statements)

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“…Although the recent study demonstrated KLF12 enhances anoikis resistance of lung metastatic cancer cells via regulating cell cycle progression [61], our findings in this study showed another mechanism of that the loss of KLF12 elevating the expression of survivin and its related intrinsic apoptotic pathway. Overexpression of survivin, which belongs to the inhibitor of apoptosis (IAP) proteins, may lead to cancer cell invasiveness, poor patient prognosis and low survival rates [62, 63]. The survivin anti-apoptotic network is mediated through the survivin-XIAP complex, which subsequently inhibits the activation of caspase-9 and the cleavage of caspase3 and PARP.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-141 enhances anoikis resistance in metastatic progression of ovarian cancer through targeting KLF12/Sp1/survivin axis

et al. 2017

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BackgroundCancer metastasis is determined by the formation of the metastatic niche and the ability of cancer cells to adapt to microenvironmental stresses. Anoikis resistance is a fundamental feature of metastatic cancer cell survival during metastatic cancer progression. However, the mechanisms underlying anoikis resistance in ovarian cancer are still unclear.MethodsExpressions of miRNA-141 and its downstream targets were evaluated by qPCR, Western blotting, Immunohistochemical (IHC) and in situ hybridization (ISH) assays. The luciferase assays were used to prove KLF12 as the downstream target of miR-141. The cDNA microarray and apoptotic protein arrays were used to identify the targets of miR-141 and KLF12. The competition of KLF12 and Sp1 on survivin promoter was examined by ChIP assay. IHC analysis on ovarian cancer tissue array was used to evaluate the expressions of KLF12 and miR-141 and to show the clinical relevance. The functional studies were performed by in vitro and in vivo tumorigenic assays.ResultsEnforced expression of miR-141 promotes, while knockdown of miR-141 expression inhibits, cell proliferation, anchorage-independent capacity, anoikis resistance, tumor growth and peritoneal metastases of ovarian cancer cells. Bioinformatics and functional analysis identified that Kruppel-related zinc finger protein AP-2rep (KLF12) is directly targeted by miR-141. Consistent with this finding, knockdown of KLF12 phenocopied the effects of miR-141 overexpression in ovarian cancer cells. In contrast, restoration of KLF12 in miR-141-expressing cells significantly attenuated anoikis resistance in ovarian cancer cells via interfering with Sp1-mediated survivin transcription, which inhibits the intrinsic apoptotic pathway and is crucial for ovarian cancer cell survival, anoikis resistance and peritoneal metastases. Immunohistochemical (IHC) and in situ hybridization (ISH) assays confirmed that miRNA-141 expression is inversely correlated with KLF12 expression and significantly associated with advanced ovarian cancers accompanied with distal metastases, underscoring the clinical relevance of our findings.ConclusionsOur data identify a novel signaling axis of miR-141/KLF12/Sp1/survivin in enhancing anoikis resistance and likely serves as a potential therapeutic target for metastatic ovarian cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0582-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-141 enhances anoikis resistance in metastatic progression of ovarian cancer through targeting KLF12/Sp1/survivin axis

et al. 2017

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“…Similarly, survivin expression was observed in most human NHLs of various morphological subtypes and often exceeded 70%-80% of examined cases. In the study of Gu and Lin (2004) the differences of survivin expression between high and low grade lymphomas were found. In the latter group survivin expression was observed in 20%-40% of cases depending of its histological subtype.…”

Section: Discussionmentioning

confidence: 99%

Survivin expression in canine lymphomas in relation with proliferative markers

Sokołowska¹,

Urbańska²,

Gizinski³

et al. 2015

Polish Journal of Veterinary Sciences

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Survivin is a member of apoptosis inhibiting proteins family. Apart from its antiapoptotic activity it plays a critical role in regulating the cell cycle and mitosis. It is overexpressed in most human malignancies. While the prognostic significance of survivin expression is widely investigated in human non-Hodgkin's lymphomas, little is known about its expression in canine lymphomas. The aim of the study was to evaluate the expression of survivin in canine lymphomas in relation to proliferation markers (mitotic index and percentage of Ki67-positive cells). Survivin was found in all examined lymphomas belonging to 6 different morphological subtypes with nuclear immunoreactivity. In most of lymphomas (18/25) survivin expression ranged 10%-25% of positive cells. Only single cases had lower (0-10% positive cells, 1/25) or higher (25-50% and >50% positive cells, 5/25 and 1/25, respectively) index of survivin. Neither mitotic index nor proliferative index correlated with survivin expression when the values quantified randomly in whole specimens were compared. However, when survivin expression were quantified in selected tumor areas of low and high proliferation activity the high correlations between survivin expression and proliferation index were found. The results indicated that survivin is commonly expressed in canine lymphomas. Nuclear labelling together with the relation of its expression and proliferative activity in highly proliferative areas of neoplastic tissue suggest a potential role of survivin in cell cycle activation in canine lymphoma cells. However, further studies of the relation between expression of survivin and other proteins involved in cell cycle regulation are needed. Moreover, the results suggest that survivin may pose the therapeutic target in canine lymphomas.

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“…Besides being overexpressed in oral cancers, survivin was found to be over-expressed in patients with colorectal carcinoma and lymphoma (20). Two studies revealed that expression of survivin was significantly higher in adenomatous polyps and adenocarcinoma as compared to normal colorectal mucosa (21,22).…”

Section: The Expression Of Survivin In Human Cancersmentioning

confidence: 99%

Investigations of survivin: the past, present and future

Cheung¹

2011

Front Biosci

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Survivin is a member of the inhibitors-of-apoptosis protein (IAPs) family. It promotes cell survival through interference with multiple cell cycle-related proteins such as INCENP and Aurora B kinase. Survivin also inhibits cell death through interference with both caspase-dependent and -independent cell apoptosis. Interestingly, recent evidence suggests that survivin may also play a role in the regulation of cancer cell autophagy. At the clinical level, studies on clinical specimens have shown that survivin expression is up-regulated in various human cancers and its up-regulation is associated with tumour resistance to both chemotherapy and radiation therapy. On the basis of these findings, survivin has been proposed as an attractive target for new anti-cancer interventions. However, despite the role that survivin plays in cancer cell survival and anti-drug response, the development of survivin inhibitors is relatively slow as compared to other therapeutic inhibitors for cancer treatment. In this review, the relationships between survivin expression and the causation of drug resistance in cancers are re-addressed. This review also summarizes the recent development of survivin inhibitors for clinical usage.

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Analysis of Survivin Expression in the Subtypes of Lymphoma

Cited by 8 publications

References 8 publications

MicroRNA-141 enhances anoikis resistance in metastatic progression of ovarian cancer through targeting KLF12/Sp1/survivin axis

MicroRNA-141 enhances anoikis resistance in metastatic progression of ovarian cancer through targeting KLF12/Sp1/survivin axis

Survivin expression in canine lymphomas in relation with proliferative markers

Investigations of survivin: the past, present and future

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