The feedback loop of LITAF and BCL6 is involved in regulating apoptosis in B cell non-Hodgkin's-lymphoma

Shi, Yi; Kuai, Yue; Luo, Lei; Weng, Yuanyuan; Berberich‐Siebelt, Friederike; Zhang, Xinxia; Wang, Jinjie; Zhou, Yuan; Jiang, Xin; Ren, Guoping; Pan, Hongyang; Mao, Zhengrong; Ren, Zhimin

doi:10.18632/oncotarget.12680

Cited by 12 publications

(9 citation statements)

References 44 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Zhou et al (2011). LITAF is a DNA-binding protein and is well known for its role as a transcriptional regulator of TNF-a (Shi et al, 2016). ATM and TNF-a expression have previously been correlated: It was shown that in apoptosis, TNF-a activated caspase-3, which cleaved and downregulated ATM (Hotti et al, 2000;Smith et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Affymetrix data were deposited to the GEO database. Of the 12 tumor suppressor gene candidates, five were previously described to be involved in proliferation, cell death, or radiation response in various cancer types: LITAF, RASSF2, PHLPP2, RUNX3, and TP53INP1 (Huang et al, 2009;Jiang et al, 2010;Sakakura et al, 2007;Sandor et al, 2015;Shi et al, 2016;Wei et al, 2012;Yamamura et al, 2006;Zhou et al, 2011). Expression levels between PC3 and DU145 control and miR-106a cells were compared using qRT-PCR (Fig.…”

Section: Mir-106a Promotes Radioresistance and Tumor Aggression By Tamentioning

confidence: 99%

See 1 more Smart Citation

miRNA‐106a and prostate cancer radioresistance: a novel role for LITAF in ATM regulation

et al. 2018

View full text Add to dashboard Cite

Recurrence of high‐grade prostate cancer after radiotherapy is a significant clinical problem, resulting in increased morbidity and reduced patient survival. The molecular mechanisms of radiation resistance are being elucidated through the study of microRNA (miR) that negatively regulate gene expression. We performed bioinformatics analyses of The Cancer Genome Atlas (TCGA) dataset to evaluate the association between miR‐106a and its putative target lipopolysaccharide‐induced TNF‐α factor (LITAF) in prostate cancer. We characterized the function of miR‐106a through in vitro and in vivo experiments and employed transcriptomic analysis, western blotting, and 3′UTR luciferase assays to establish LITAF as a bona fide target of miR‐106a. Using our well‐characterized radiation‐resistant cell lines, we identified that miR‐106a was overexpressed in radiation‐resistant cells compared to parental cells. In the TCGA, miR‐106a was significantly elevated in high‐grade human prostate tumors relative to intermediate‐ and low‐grade specimens. An inverse correlation was seen with its target, LITAF. Furthermore, high miR‐106a and low LITAF expression predict for biochemical recurrence at 5 years after radical prostatectomy. miR‐106a overexpression conferred radioresistance by increasing proliferation and reducing senescence, and this was phenocopied by knockdown of LITAF. For the first time, we describe a role for miRNA in upregulating ATM expression. LITAF, not previously attributed to radiation response, mediates this interaction. This route of cancer radioresistance can be overcome using the specific ATM kinase inhibitor, KU‐55933. Our research provides the first report of miR‐106a and LITAF in prostate cancer radiation resistance and high‐grade disease, and presents a viable therapeutic strategy that may ultimately improve patient outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Mir-106a Promotes Radioresistance and Tumor Aggression By Tamentioning

confidence: 99%

miRNA‐106a and prostate cancer radioresistance: a novel role for LITAF in ATM regulation

et al. 2018

View full text Add to dashboard Cite

show abstract

“…After cultures with PU-H71 or DMSO for 48 h, OCI-Ly10 cells were washed twice in PBS, spread onto slides, air dried and fixed in acetone at − 20 °C for 15 min. Immunofluorescence staining was performed as described previously [ 13 ]. After treatment of 0.3% Triton X-100 (KeyGen Biotech) for 10 min, the slides were blocked with Goat serum (Boster Biological Technology) for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…BCL6 might function as a stress response gene that forms part of a larger, post-transcriptionally regulated program governed by Hsp90 [ 12 ]. In the pathogenesis of Diffuse large B-cell lymphoma (DLBCL), BCL6 transcriptional repressor is the most frequently involved oncoprotein, which is required to sustain proliferation and survival of DLBCL cells through regulation of specific targets such as PRDM1 , c-Myc or PAX-5 [ 13 ]. However, relatively little is known about the contribution of WTAP – one further client protein of Hsp90.…”

Section: Introductionmentioning

confidence: 99%

Wilms’ tumor 1-associating protein plays an aggressive role in diffuse large B-cell lymphoma and forms a complex with BCL6 via Hsp90

et al. 2018

Self Cite

View full text Add to dashboard Cite

BackgroundWilms’ tumor 1-associating protein (WTAP) is a nuclear protein, which is ubiquitously expressed in many tissues. Furthermore, in various types of malignancies WTAP is overexpressed and plays a role as an oncogene. The function of WTAP in diffuse large B-cell lymphoma (DLBCL), however, remains unclear.MethodsImmunohistochemistry was applied to evaluate the levels of WTAP expression in DLBCL tissues and normal lymphoid tissues. Overexpression and knock-down of WTAP in DLBCL cell lines, verified on mRNA and protein level served to analyze cell proliferation and apoptosis in DLBCL cell lines by flow cytometry. Finally, co-immunoprecipitation (Co-IP), IP, and GST-pull down assessed the interaction of WTAP with Heat shock protein 90 (Hsp90) and B-cell lymphoma 6 (BCL6) as well as determined the extend of its ubiquitinylation.ResultsWTAP protein levels were consistently upregulated in DLBCL tissues. WTAP promoted DLBCL cell proliferation and improved the ability to confront apoptosis, while knockdown of WTAP in DLBCL cell lines allowed a significant higher apoptosis rate after treatment with Etoposide, an anti-tumor drug. The stable expression of WTAP was depended on Hsp90. In line, we demonstrated that WTAP could form a complex with BCL6 via Hsp90 in vivo and in vitro.ConclusionWTAP is highly expressed in DLBCL, promoting growth and anti-apoptosis in DLBCL cell lines. WTAP is a client protein of Hsp90 and can appear in a complex with BCL6 and Hsp90 in DLBCL. Down-regulation of WTAP could improve the chemotherapeutic treatments in DLBCL.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0258-6) contains supplementary material, which is available to authorized users.

show abstract

“…Recent studies have shown that LITAF is frequently down-regulated in different types of cancer [ 20 ], including acute leukemia [ 17 ], breast cancer [ 16 , 21 ], lymphoma [ 22 , 23 ], and prostatic cancer [ 24 ], suggesting that it may function as a tumor suppressor gene. The downregulation of LITAF induces migration, increased cell viability, and colony formation in cancer cells [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

LITAF is a potential tumor suppressor in pancreatic cancer

Zhou

Huang

et al. 2017

Oncotarget

Self Cite

View full text Add to dashboard Cite

Early diagnosis of pancreatic cancer, one of the most deadly cancers with low survival rates, is difficult, and effective biomarkers are urgently needed. Lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) has been recently proposed as a potential tumor suppressor gene in several types of cancer. Here, we analyzed the biological function of LITAF in pancreatic cancer. The LITAF gene and protein levels were decreased in pancreatic tumor tissues compared with their paired adjacent non-cancerous tissues. In addition, patients with the lower LITAF protein expression had lower disease-free survival rates. The decreased LITAF expression correlated with LITAF promoter hypermethylation in pancreatic cancer cells and tissues. Moreover, promoter demethylation dose-dependently increased the LITAF transcription. Importantly, LITAF demethylation suppressed proliferation and cell cycle progression, and enhanced apoptosis of pancreatic cancer cells. Together, our results indicate that LITAF functions as a tumor suppressor gene in pancreatic cancer cells, and might serve as a novel biomarker for early diagnosis of pancreatic cancer.

show abstract

The feedback loop of LITAF and BCL6 is involved in regulating apoptosis in B cell non-Hodgkin's-lymphoma

Cited by 12 publications

References 44 publications

miRNA‐106a and prostate cancer radioresistance: a novel role for LITAF in ATM regulation

miRNA‐106a and prostate cancer radioresistance: a novel role for LITAF in ATM regulation

Wilms’ tumor 1-associating protein plays an aggressive role in diffuse large B-cell lymphoma and forms a complex with BCL6 via Hsp90

LITAF is a potential tumor suppressor in pancreatic cancer

Contact Info

Product

Resources

About