Overexpression of survivin in pediatric Hodgkin lymphoma tumor cells: Characterization of protein expression and splice-variants transcription profile

Lorenzetti, Mario Alejandro; Mosna, María Jimena; Matteo, Elena Noemí de; Lombardi, Mercedes García; Colli, Sandra; Preciado, María Victoria

doi:10.1016/j.yexmp.2019.03.005

Cited by 4 publications

(4 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Survivin can promote cell proliferation by inhibiting caspase activation and stabilizing microtubules during cell mitosis to protect cells from apoptosis (23). Previous studies have found that survivin is upregulated in a variety of human malignancies (24)(25)(26) and is associated with poor prognosis (27)(28)(29)(30), leading to proposals of survivin being used as a potential tumor marker and prognostic indicator. However, the significance of survivin in breast cancer progression remain controversial.…”

Section: Significance Of Combined Tgf-β1 and Survivin Expression On T...mentioning

confidence: 99%

Significance of combined TGF‑β1 and survivin expression on the prognosis of patients with triple‑negative breast cancer

Liu

Jiang

et al. 2022

Oncol Lett

View full text Add to dashboard Cite

Compared with other types of breast cancer, triple-negative breast cancer (TNBC) has the characteristics of rapid progression, a lack of specific molecular targets for treatment and a poor prognosis. However, based on previously published studies, TGF-β1 and survivin are potentially meaningful for the prognosis of patients with TNBC. The present study was therefore designed to measure and compare the expression of transforming growth factor-β1 (TGF-β1) and survivin in tissue samples of TNBC and non-TNBC patients in order to evaluate their ability as prognostic indicators. In total, 90 TNBC and 52 non-TNBC tissue specimens were selected, following which immunohistochemistry was used to detect the expression of TGF-β1 and survivin in the cancer tissues. Subsequently, the potential association between the expression levels of these two proteins and the clinicopathological variables was analyzed. The expression levels of TGF-β1 and survivin in TNBC tissues were found to be significantly higher compared with those in the non-TNBC tissues. In addition, the results of the present study demonstrated that TGF-β1 expression was positively associated with survivin expression in the TNBC samples, but no significant correlation was found between TGF-β1 and survivin expression in the non-TNBC samples. Kaplan-Meier (K-M) analysis was performed to assess the levels of TGF-β1 and survivin in regard to patient survival, and univariate and multivariate Cox analyses of TGF-β1 and survivin protein expression were performed to analyze the overall survival (OS) and progression-free survival (PFS) rates of patients with TNBC and non-TNBC. Although multivariate Cox analysis demonstrated that neither TGF-β1 or survivin were independent prognostic predictors of TNBC or non-TNBC, results of the K-M curve revealed that patients with TNBC with TGF-β1-and survivin-positive breast cancer exhibited shorter OS and PFS times. Multivariate Cox analysis demonstrated that in patients with TNBC, the combined expression of TGF-β1 and survivin may yield additional prognostic information, compared with patients with non-TNBC.

show abstract

Section: Significance Of Combined Tgf-β1 and Survivin Expression On T...mentioning

confidence: 99%

Significance of combined TGF‑β1 and survivin expression on the prognosis of patients with triple‑negative breast cancer

Liu

Jiang

et al. 2022

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…28−30 However, similar to other IAPs, survivin has been shown to inhibit both extrinsic and intrinsic apoptosis pathways in cell lines and animal models. 31,32 Several mechanisms have been proposed to delineate how survivin inhibits apoptosis (Figure 1C). It may prevent apoptosis induction by interacting with pro-apoptotic proteins to inhibit caspase activation.…”

Section: Introduction 1inhibitor Of Apoptosis Proteinsmentioning

confidence: 99%

“…Human survivin, the smallest member of the IAP family with a molecular weight of 16.5 kDa, consists of 142 amino acid residues and exists as a homodimer with a single BIR domain in the N-terminus, a zinc-finger fold, and an extended C-terminal helical coiled coil (Figure B) . Unlike other IAPs, which are found mainly in the cytosol and to a lesser extent in the nucleus, survivin is present in multiple subcellular locations, including the nucleus, the cytosol, mitochondria, and extracellular exosomes. − However, similar to other IAPs, survivin has been shown to inhibit both extrinsic and intrinsic apoptosis pathways in cell lines and animal models. , …”

Section: Introductionmentioning

confidence: 99%

Small Molecule Inhibitors Targeting the “Undruggable” Survivin: The Past, Present, and Future from a Medicinal Chemist’s Perspective

Cui,

Huang,

Liu

et al. 2023

J. Med. Chem.

View full text Add to dashboard Cite

“…SSVs have been shown to play a role in different many cancer processes but their role in pancreatic cancer chemotherapy resistance has not been fully elucidated. The SSVs survivin (birc5, wild type), survivin ΔEx3, survivin 2β and survivin 2α are associated with cancer progression and chemoresistance [30][31][32][33] while little has been reported in survivin 3α and survivin 3β isoforms. 34 Specifically, it has been reported that increased levels of the 2β SSV plays the most prominent SSV role in cancer chemoresistance.…”

Section: Introductionmentioning

confidence: 99%

Survivin Splice Variant 2β Enhances Pancreatic Ductal Adenocarcinoma Resistance to Gemcitabine

Fuller¹,

Kabagwira²,

Vallejos³

et al. 2022

OTT

View full text Add to dashboard Cite

Background Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with poor prognosis, as it is difficult to predict or circumvent, and it develops chemoresistance quickly. One cellular mechanism associated with chemoresistance is alternative splicing dysfunction, a process through which nascent mRNA is spliced into different isoforms. Survivin (Baculoviral IAP Repeat-Containing Protein 5 (BIRC5)), a member of the inhibitor of apoptosis (IAP) protein family and a cell cycle-associated oncoprotein, is overexpressed in most cancers and undergoes alternative splicing (AS) to generate six different splicing isoforms. Methods To determine if survivin splice variants (SSV) could be involved in PDAC chemoresistance, a Gemcitabine (Gem) resistant (GR) cell line, MIA PaCa-2 GR, was created and assessed for its SSV levels and their potential association with GR. Cross-resistance was assessed in MIA-PaCa-2 GR cells to FIRINOX (5-fluorouracil (5-FU), irinotecan, and oxaliplatin). Once chemoresistance was confirmed, RT-qPCR was used to assess the expression of survivin splice variants (SSVs) in PDAC cell lines. To confirm the effect of SSVs on chemoresistance, we used siRNA to knockdown all SSVs or SSV 2β. Results The MIA PaCa-2 GR cell line was 40 times more resistant to Gem and revealed increased resistance to FIRINOX (5-fluorouracil (5-FU), irinotecan, and oxaliplatin); when compared to the parental MIA-PaCa-2 cells. RT-qPCR studies revealed an 8-fold relative expression increase in SSV 2β and a 2- to 8-fold increase in the other five SSVs in the GR cells. Knockdown of all SSV or SSV 2β only, using small inhibitory RNA (siRNA), sensitized the GR cells to Gem, indicating that these SSVs play a role in PDAC chemoresistance. Conclusion These findings provide evidence for the potential role of SSV 2β and other SSVs in innate and acquired PDAC chemoresistance. We also show that the expression of SSVs is not affected by the type of chemoresistance, therefore targeting survivin splice variants in combination with chemotherapy could benefit a wide range of patients.

show abstract

Overexpression of survivin in pediatric Hodgkin lymphoma tumor cells: Characterization of protein expression and splice-variants transcription profile

Cited by 4 publications

References 34 publications

Significance of combined TGF‑β1 and survivin expression on the prognosis of patients with triple‑negative breast cancer

Significance of combined TGF‑β1 and survivin expression on the prognosis of patients with triple‑negative breast cancer

Small Molecule Inhibitors Targeting the “Undruggable” Survivin: The Past, Present, and Future from a Medicinal Chemist’s Perspective

Survivin Splice Variant 2β Enhances Pancreatic Ductal Adenocarcinoma Resistance to Gemcitabine

Contact Info

Product

Resources

About