Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells

Liang, Xin; Shi, Haiyang; Yang, Liyan; Qiu, Cen; Lin, Shengchao; Qi, Yanfei; Li, Jiyu; Zhao, Aizhi; Liu, Jianwen

doi:10.1038/bjc.2017.32

Cited by 27 publications

(26 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In gastric cancer, PTBP3 contributes to the cancer metastasis by mediating CAV1 alternative splicing (Liang et al, 2018). Inhibition of PTBP3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5-fluorouracil in gastric cancer cells (Liang et al, 2017). The present study demonstrated, for the first time, that miR-29a/PTBP3 is regulated by ILF3-AS1 in GC.…”

Section: Discussionsupporting

confidence: 57%

WGCNA Co-Expression Network Analysis Reveals ILF3-AS1 Functions as a CeRNA to Regulate PTBP1 Expression by Sponging miR-29a in Gastric Cancer

Ren

Shang

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

Gastric cancer (GC) is one of the most common types of human cancers worldwide. However, the detail mechanisms underlying GC progression remained to be investigated. The present study identified 2823 differently expressed mRNAs and 441 differently expressed lncRNAs in GC. WGCNA was conducted to identify highly correlated lncRNAs and mRNAs. Bioinformatics analysis observed that these dysregulated lncRNAs were significantly associated with the regulation of angiogenesis, cell division, cell-cell adhesion, blood vessel development, adaptive immune response, gastric acid secretion, immune response. Co-expression analysis identified ILF3-AS1 was a key lncRNA involved in regulating GC progression. Loss of function assays showed that knockdown of ILF3-AS1 significantly suppressed GC cell proliferation and metastasis. Mechanically, the results indicate that ILF3-AS1 could enhance PTBP3 expression as an miR-29a sponge, thereby promoting the proliferation and metastasis of GC cells. Our work suggests that the ILF3-AS1/miR-29a/PTBP3 axis may be a potential target for the clinical diagnosis and treatment of GC.

show abstract

Section: Discussionsupporting

confidence: 57%

WGCNA Co-Expression Network Analysis Reveals ILF3-AS1 Functions as a CeRNA to Regulate PTBP1 Expression by Sponging miR-29a in Gastric Cancer

Ren

Shang

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…1b ). These results were consistent with our previous study 31 . Our previous study also found that PTBP3 expression is associated with lymph node metastasis.…”

Section: Resultssupporting

confidence: 94%

PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing

et al. 2018

Self Cite

View full text Add to dashboard Cite

Polypyrimidine tract-binding protein 3 (PTBP3) is an essential RNA-binding protein with roles in RNA splicing, 3′ end processing and translation. Although increasing evidence implicates PTBP3 in several cancers, its role in gastric cancer metastasis remains poorly explored. In this study, we found that PTBP3 was upregulated in the gastric cancer tissues of patients with lymph node metastasis. Patients with high PTBP3 expression levels had significantly shorter survival than those with low PTBP3 expression. Overexpression/knockdown of PTBP3 expression had no effect on proliferation, whereas it regulated migration and invasion in vitro. In addition, when a mouse xenotransplant model of MKN45 was established, knockdown of PTBP3 in MKN45 cells caused the formation of tumours that were smaller in size than their counterparts, with suppression of tumour lymphangiogenesis and metastasis to regional lymph nodes. Furthermore, we identified caveolin 1 (CAV1) as a downstream target of PTBP3. RNA immunoprecipitation (RIP) assays and dual-luciferase reporter gene assays indicated that PTBP3 interacted with the CU-rich region of the CAV1 gene to downregulate CAV1α expression. Knockdown of CAV1α abrogated the reduction of FAK and Src induced by PTBP3 knockdown. In summary, our findings provide experimental evidence that PTBP3 may function as a metastatic gene in gastric cancer by regulating CAV1 through alternative splicing.

show abstract

“…Both cell death and cellular senescence are important responses to stress-associated stimuli. It was demonstrated that 5-FU exerts anticancer effects mainly by inhibiting tumor cell proliferation, activating Bax and P53, and/or caspase-dependent mechanism [ 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. Annexin V/Propidium iodide (PI) staining assay is commonly applied to discern necrotic cells and apoptotic cells, further to quantify apoptosis.…”

Section: Resultsmentioning

confidence: 99%

Angelica sinensis Polysaccharides Ameliorate Stress-Induced Premature Senescence of Hematopoietic Cell via Protecting Bone Marrow Stromal Cells from Oxidative Injuries Caused by 5-Fluorouracil

Xiao

Xiong

Song

et al. 2017

IJMS

View full text Add to dashboard Cite

Myelosuppression is the most common complication of chemotherapy. Decline of self-renewal capacity and stress-induced premature senescence (SIPS) of hematopoietic stem cells (HSCs) induced by chemotherapeutic agents may be the cause of long-term myelosuppression after chemotherapy. Whether the mechanism of SIPS of hematopoietic cells relates to chemotherapeutic injury occurred in hematopoietic microenvironment (HM) is still not well elucidated. This study explored the protective effect of Angelica sinensis polysaccharide (ASP), an acetone extract polysaccharide found as the major effective ingredients of a traditional Chinese medicinal herb named Chinese Angelica (Dong Quai), on oxidative damage of homo sapiens bone marrow/stroma cell line (HS-5) caused by 5-fluorouracil (5-FU), and the effect of ASP relieving oxidative stress in HM on SIPS of hematopoietic cells. Tumor-suppressive doses of 5-FU inhibited the growth of HS-5 in a dose-dependent and time-dependent manner. 5-FU induced HS-5 apoptosis and also accumulated cellular hallmarks of senescence including cell cycle arrest and typical senescence-associated β-galactosidase positive staining. The intracellular reactive oxygen species (ROS) was increased in 5-FU treated HS-5 cells and coinstantaneous with attenuated antioxidant capacity marked by superoxide dismutase and glutathione peroxidase. Oxidative stress initiated DNA damage indicated by increased γH2AX and 8-OHdG. Oxidative damage of HS-5 cells resulted in declined hematopoietic stimulating factors including stem cell factor (SCF), stromal cell-derived factor (SDF), and granulocyte-macrophage colony-stimulating factor (GM-CSF), however, elevated inflammatory chemokines such as RANTES. In addition, gap junction channel protein expression and mediated intercellular communications were attenuated after 5-FU treatment. Significantly, co-culture on 5-FU treated HS-5 feeder layer resulted in less quantity of human umbilical cord blood-derived hematopoietic cells and CD34+ hematopoietic stem/progenitor cells (HSPCs), and SIPS of hematopoietic cells. However, it is noteworthy that ASP ameliorated SIPS of hematopoietic cells by the mechanism of protecting bone marrow stromal cells from chemotherapeutic injury via mitigating oxidative damage of stromal cells and improving their hematopoietic function. This study provides a new strategy to alleviate the complication of conventional cancer therapy using chemotherapeutic agents.

show abstract

Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells

Cited by 27 publications

References 42 publications

WGCNA Co-Expression Network Analysis Reveals ILF3-AS1 Functions as a CeRNA to Regulate PTBP1 Expression by Sponging miR-29a in Gastric Cancer

WGCNA Co-Expression Network Analysis Reveals ILF3-AS1 Functions as a CeRNA to Regulate PTBP1 Expression by Sponging miR-29a in Gastric Cancer

PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing

Angelica sinensis Polysaccharides Ameliorate Stress-Induced Premature Senescence of Hematopoietic Cell via Protecting Bone Marrow Stromal Cells from Oxidative Injuries Caused by 5-Fluorouracil

Contact Info

Product

Resources

About