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1.
Mol Cell Biochem ; 476(3): 1455-1465, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33389496

ABSTRACT

Melanoma ranks second in aggressive tumors, and the occurrence of metastasis in melanoma results in a persistent drop in the survival rate of patients. Therefore, it is very necessary to find a novel therapeutic method for treating melanoma. It has been reported that lncRNA XIST could promote the tumorigenesis of melanoma. However, the mechanism by which lncRNA XIST regulates the progression of melanoma remains unclear. The proliferation of A375 cells was measured by clonal formation. Cell viability was detected by MTT assay. Flow cytometry was performed to detect cell apoptosis and cycle. The level of GINS2, miR-23a-3p, and lncRNA XIST was investigated by qRT-PCR. Protein level was detected by Western blot, and the correctness of prediction results was confirmed by Dual luciferase. In present study, GINS2 and lncRNA XIST were overexpressed in melanoma, while miR-23a-3p was downregulated. Silencing of GINS2 or overexpression of miR-23a-3p reversed cell growth and promoted apoptosis in A375 cells. Mechanically, miR-23a-3p directly targeted GINS2, and XIST regulated GINS2 level though mediated miR-23a-3p. Moreover, XIST exerted its function on cell proliferation, cell viability, and promoted the cell apoptosis of A375 cells though miR-23a-3p/GINS2 axis. LncRNA XIST significantly promoted the tumorigenesis of melanoma via sponging miR-23a-3p and indirectly targeting GINS2, which can be a potential new target for treating melanoma.


Subject(s)
Apoptosis , Chromosomal Proteins, Non-Histone/biosynthesis , Gene Expression Regulation, Neoplastic , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , Cell Cycle , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cell Survival , Down-Regulation , Gene Expression Regulation , Gene Silencing , HEK293 Cells , Humans , Melanocytes/metabolism , Melanoma/metabolism , MicroRNAs/genetics , Signal Transduction , Tetrazolium Salts/pharmacology , Thiazoles/pharmacology
2.
Zhonghua Yi Xue Za Zhi ; 93(6): 464-8, 2013 Feb 05.
Article in Zh | MEDLINE | ID: mdl-23660270

ABSTRACT

OBJECTIVE: To explore the anti-tumor effects of resveratrol (Res) upon human skin squamous cell carcinoma A431 xenograft in nude mice and elucidate the regulatory mechanisms of survivin and caspase-3. METHODS: The model of human skin squamous cell carcinoma (A431) xenograft in nude mice was established. And the animals were randomly divided into saline-negative control, cyclophosphamide (CTX) positive control, Res high-, medium- and low-dosage and blank control groups (n = 10 each). After drug intervention, tumor-bearing mice were sacrificed. The tumor growth curve was plotted and the Res inhibition rate calculated by terminal tumor weight. The morphological changes of tumor cell among groups were observed by hematoxylin and eosin staining; cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling TUNEL; the impact of Res upon the protein expressions of survivin and caspase-3 in tumor issues was observed by Western blot. Analysis of variance and Pearson's correlation were employed for statistical analyses. RESULTS: (1) By the end of treatment, the tumor volume of CTX, Res high-, medium-, low-dosage, saline-negative control and blank control groups were (1154 ± 255), (1002 ± 115), (1207 ± 176), (1342 ± 211), (1642 ± 226), (1564 ± 156) mm(3) respectively, and tumor weight of CTX, Res high-, medium-, low-dosage, saline-negative control and blank control groups (1.84 ± 0.30), (1.72 ± 0.39), (1.96 ± 0.40), (2.67 ± 0.73), (3.16 ± 0.52), (3.33 ± 0.59) g respectively. Through analysis of variance, the tumor volume and weight of Res high-, medium-, low-dosage groups were smaller than those of saline-negative control and blank control groups (all P < 0.05). The inhibition rate of Res high-, medium- and low-dosage groups were 45.57%, 37.97% and 15.51% respectively. (2) The apoptosis index of the above groups were 36.79% ± 8.86%, 33.15% ± 6.00%, 18.09% ± 3.92%, 10.53% ± 4.20%, 3.87% ± 1.63%, 2.73% ± 1.61%. Through analysis of variance, the apoptosis index of Res groups were higher than those of saline-negative control and blank control groups (all P < 0.05). (3) The protein expression of survivin/ß-actin of each group were 0.48 ± 0.20, 0.19 ± 0.11, 0.22 ± 0.12, 0.28 ± 0.24, 0.98 ± 0.41, 0.85 ± 0.34. The protein expression of caspase-3/ß-actin of each group were 0.42 ± 0.09, 0.31 ± 0.10, 0.31 ± 0.07, 0.22 ± 0.08, 0.14 ± 0.04, 0.13 ± 0.05 respectively. Through analysis of variance, the protein expression of survivin of Res groups was lower than those of the saline-negative control and blank control groups (all P < 0.05). And the protein expression of caspase-3 of Res groups were higher than those of the saline-negative control and blank control group (all P < 0.05). Through Pearson's analysis, the protein expression of survivin and caspase-3 had no correlation (r = -0.279, P > 0.05). CONCLUSIONS: Res inhibits the growth of human skin squamous cell carcinoma A431 xenograft in nude mice. And its mechanism may be associated with the apoptosis of tumor cell through the depression of survivin and the activation of caspase-3.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Skin Neoplasms/metabolism , Stilbenes/pharmacology , Animals , Apoptosis , Caspase 3/metabolism , Cell Line, Tumor , Female , Humans , Inhibitor of Apoptosis Proteins/metabolism , Mice , Mice, Nude , Resveratrol , Survivin , Xenograft Model Antitumor Assays
3.
Med Oncol ; 29(3): 1879-85, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22135002

ABSTRACT

Recent studies have demonstrated that N-Myc downstream-regulated gene 2 (NDRG2) may reduce the metastatic potential of breast cancer and hepatocellular carcinoma cells by regulating the expression of CD24, which is expressed in a large variety of solid tumors. The aim of this study was to clarify the clinical value of NDRG2 and CD24 expression in primary gallbladder carcinoma (GBC). One hundred and thirty GBC tissues were evaluated by immunohistochemistry for NDRG2 and CD24 expression. The associations of NDRG2 and CD24 expression with the clinicopathological characteristics and the overall survival of patients with GBC were analyzed. NDRG2 and CD24 were positively expressed in 49/130 (37.69%) and 107/130 (82.31%) of GBC tissues, respectively. In addition, the tumors with the down-regulation of NDRG2 and the up-regulation of CD24 more frequently had lymph node metastasis and lymphovascular invasion. Moreover, the tumors with the down-regulation of NDRG2 and the up-regulation of CD24 tended to show deeper invasion depth and higher TNM stage. There was a negative correlation between NDRG2 expression and CD24 expression in GBC tissues (r = -0.86, P < 0.001). The patients with NDRG2 negative expression correlated with poor prognosis of GBC (P = 0.01), as opposed to CD24 (P = 0.01). The survival rate of the patients with NDRG2-/CD24+ expression was the lowest (P < 0.001), and conjoined expression of NDRG2-/CD24+ was an independent prognostic indicator of GBC (P = 0.003). Our data suggest that NDRG2 down-regulation or CD24 up-regulation is an important feature of GBC. A combined detection of NDRG2/CD24 co-expression may benefit us in prediction of the prognosis in GBC.


Subject(s)
Biomarkers, Tumor/analysis , CD24 Antigen/biosynthesis , Carcinoma/metabolism , Gallbladder Neoplasms/metabolism , Tumor Suppressor Proteins/biosynthesis , CD24 Antigen/analysis , Carcinoma/mortality , Carcinoma/pathology , Down-Regulation , Female , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/pathology , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Staging , Prognosis , Tumor Suppressor Proteins/analysis , Up-Regulation
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