CYLD downregulates Livin and synergistically improves gemcitabine chemosensitivity and decreases migratory/invasive potential in bladder cancer: the effect is autophagy-associated

Yin, Lei; Liu, Shuai; Li, Chensheng; Ding, Sentai; Bi, Dongbin; Niu, Zhihong; Han, Liping; Li, Wenjia; Gao, Dexuan; Liu, Zheng; Lü, Jiaju

doi:10.1007/s13277-016-5157-0

Cited by 12 publications

(6 citation statements)

References 55 publications

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“…Therefore, in the present study, we investigated the role of Livin in determining susceptibility to commonly used chemotherapeutic drugs, such as docetaxel, cisplatin and 5-FU, in human HNSCC cell lines. Although several studies have described that Livin contribute to the resistance of various chemotherapeutic drugs including cisplatin in various cancers (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34), the present study is the first to demonstrate the correlation between Livin and chemoresistance in human HNSCC.…”

Section: Introductionmentioning

confidence: 53%

“…Livin, a recently discovered IAP, is composed of a single BIR domain and a RING motif (9). Livin has been implicated in chemoresistance in various cancers (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). It has been reported to play a role in resistance to cisplatin in bladder cancer, renal carcinoma, gastic cancer, hepatocellular carcinoma, lung adenocarcinoma/ non-small cell carcinoma, osteosarcoma, colon cancer and ovarian carcinoma (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)31).…”

Section: Discussionmentioning

confidence: 99%

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Livin enhances chemoresistance in head and neck squamous cell carcinoma

et al. 2017

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Abstract. The responsiveness of head and neck squamous cell carcinoma (HNSCC) to chemotherapy widely affects prognosis. Overcoming chemoresistance is necessary to improve prognoses in patients with advanced HNSCC. Evasion of apoptosis by cancer cells is a major cause of chemoresistance. Livin, a member of the human inhibitors of apoptosis protein family, is highly expressed in various human cancer tissues and is associated with tumor progression and poor prognosis in human cancers. The aim of the present study was to evaluate the role of Livin in the susceptibility to popularly used chemotherapeutic drugs such as cisplatin, 5-fluorouracil (FU) and docetaxel in human HNSCC cell lines (SNU1041, PCI1 and PCI50 cells). Reverse transcription polymerase chain reaction and western blotting were performed to determine mRNA and protein expression levels. Cell viability and apoptosis assays were used to assess the functional effects of small-interfering RNA-mediated knockdown of Livin. Each HNSCC cell line had different sensitivity to chemotherapeutic drugs. Livin knockdown significantly enhanced cytotoxicity to cisplatin, 5-FU and docetaxel in human HNSCC cells. Livin knockdown induced apoptosis and enhanced chemotherapyinduced apoptosis to cisplatin, 5-FU and docetaxel. Consistent with this, Livin-knockdown cells showed greater expression of cleaved caspases-3 and -7 and poly(ADP-ribose)polymerase compared with that in control cells after cisplatin, 5-FU, or docetaxel treatment. In conclusion, our results suggest that siRNA-mediated Livin knockdown enhanced the chemosensitivity of the three HNSCC cell lines to cisplatin, 5-FU and docetaxel. Although further investigations are required to support these findings, our results demonstrated that novel therapeutic strategies with combined use of siRNA targeting Livin and chemotherapeutic agents may have applications in the treatment of advanced HNSCC.

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Section: Introductionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Livin enhances chemoresistance in head and neck squamous cell carcinoma

et al. 2017

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“…It is well known that abnormal expression of mi-croRNAs can regulate some pivotal biological behaviors, including chemotherapy resistance, which promoted chemotherapy failure and caused a poor prognosis [19][20][21][22][23][24][25]. This study firstly found that miR-130b was highly expressed in doxorubicin-insensitive BUC tissues and cell lines, which indicated that the aberrant expression of miR-130b was involved in chemotherapy resistance of BUC and its up-expression was negatively related to doxorubicin sensitivity in BUC.…”

Section: Discussionmentioning

confidence: 72%

Knockdown of microRNA-130b improves doxorubicin sensitivity in bladder urothelial carcinoma by negatively regulating cylindromatosis expression

Zhang

2021

Arch Med Sci

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Introduction: Chemotherapeutic resistance reduces the sensitivity of bladder urothelial carcinoma (BUC) to chemotherapeutic drugs and contributes a barrier leading to treatment failure. The purpose of this research project is to investigate the regulatory effects of miR-130b on chemotherapeutic drug resistance of BUC and its mechanism. Material and methods: The relative expression of miRNA-130b and cylindromatosis (CYLD) was examined using real-time quantitative PCR. The cell proliferation and doxorubicin sensitivity were detected with the enhanced CCK-8 assay. The specific combination of miR-130b and CYLD was verified with the luciferase reporter gene assay. Protein expression was detected by Western blot. Results: Our study found that miR-130b was up-regulated in doxorubicin-insensitive BUC tissues and cell lines, and its high expression was negatively related to doxorubicin sensitivity in BUC. The miR-130b knockdown reduced the IC 50 of doxorubicin and improved doxorubicin sensitivity of J82/Dox and T24/Dox cells. For the regulation mechanism analysis of miR-130b, bioinformatics analysis software was used to predict the potential targets of miR-130b, including the CYLD gene. The following luciferase activities assay, quantitative real time-PCR and western blot identified the CYLD gene as a target of miR-130b. Knockdown of CYLD reversed miR-130b's regulatory roles in doxorubicin sensitivity in J82/Dox and T24/Dox cells. Conclusions: High expression of miR-130b is negatively related to doxorubicin sensitivity in BUC, and knockdown of miR-130b improves doxorubicin sensitivity in BUC by negatively regulating CYLD expression. Our findings will provide guidance for the clinical chemotherapy of BUC.

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“…Huang et al [21] found that inhibition of autophagic flux to enhance the efficiency of GEM in GEM-resistant BC cells. In addition, we have identified many studies reporting that the mechanism of action for mitigating GEM resistance is associated with autophagy [22,23] . Interestingly, it was reported that a novel protein phosphatase, Completer's Transactivated Protein 1 (CSTP1), interacts with and specifically dephosphorylates Akt at Ser473 in vivo and in vitro to arrest cell cycle progression and promote apoptosis, and that the Ser473 site of Akt is a major cellular target of CSTP1, the expression of which is selectively down-regulated in non-invasive BC tissues [24] .…”

Section: Resultsmentioning

confidence: 99%

Role and Molecular Mechanisms of S100A9 Underlying Gemcitabine Chemoresistance in Bladder Cancer

Ma,

Zhang

2024

IJPS

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Bladder cancer cells become resistant to gemcitabine chemotherapy, S100A9 is involved in cancer progression and associated with chemo resistance, but the mechanism of S100A9's role in gemcitabine chemo resistance remains unknown. In this study, we investigated the role and mechanism of S100A9 in gemcitabine resistance in bladder cancer cells to provide a new therapeutic reference for gemcitabine resistance in bladder cancer cells. Induction of gemcitabine-resistant bladder cancer cells lines RT112, KU7, T24, lentiviral transfection of S100A9 in drug-resistant cells. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assay and clone formation assay were used to detect cell proliferation, transwell assay was used to detect cell migration and invasion, flow cytometry was used to detect apoptosis level, Western blot to detect apoptosis-related proteins and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway. S100A9 transcription and translation levels were significantly elevated in gemcitabine-resistant bladder cancer cells compared with bladder cancer cells. Compared with the empty group, the si-S100A9 group showed a significant decrease in the survival rate of gemcitabine-resistant cells, a significant decrease in the levels of Bcl-2-associated X protein, cleaved caspase-3, phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin protein, the number of clone formation, the number of cells migrating and invading. As well as a significant increase in the rate of apoptosis and the level of B-cell lymphoma 2 protein. Compared with the S100A9 group, the cell survival rate in gemcitabine-resistant bladder cancer cells were decreased in the S100A9+LY294002 group. S100A9 is highly expressed in gemcitabine-resistant bladder cancer cells; S100A9 promotes gemcitabine resistance in bladder cancer cells by targeting and excite the phosphatidylinositol-3kinase/protein kinase B/mammalian target of rapamycin pathway.

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CYLD downregulates Livin and synergistically improves gemcitabine chemosensitivity and decreases migratory/invasive potential in bladder cancer: the effect is autophagy-associated

Cited by 12 publications

References 55 publications

Livin enhances chemoresistance in head and neck squamous cell carcinoma

Livin enhances chemoresistance in head and neck squamous cell carcinoma

Knockdown of microRNA-130b improves doxorubicin sensitivity in bladder urothelial carcinoma by negatively regulating cylindromatosis expression

Role and Molecular Mechanisms of S100A9 Underlying Gemcitabine Chemoresistance in Bladder Cancer

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