|
1
|
Ding J, Zhang L, Chen S, Cao H, Xu C, Wang X. lncRNA CCAT2 Enhanced Resistance of Glioma Cells Against Chemodrugs by Disturbing the Normal Function of miR-424. Onco Targets Ther 2020; 13:1431-1445. [PMID: 32110042 PMCID: PMC7034969 DOI: 10.2147/ott.s227831] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Accepted: 11/28/2019] [Indexed: 12/14/2022] Open
Abstract
Background Aggressive metastasis of tumor cells assumed a constructive role in strengthening chemoresistance of tumors, so this investigation was intended to elucidate if lncRNA CCAT2 sponging downstream miR-424 regulated chemotolerance of glioma cells by boosting metastasis of glioma cells. Methods One hundred and twenty-eight pairs of glioma tissues and corresponding adjacent tissues were resected from glioma patients during their operation, and we also purchased a series of glioma cell lines, including U251, U87, A172 and SHG44. Furthermore, pcDNA3.1-CCAT2, si-CCAT2, miR-424 mimic and miR-424 inhibitor were transfected into SHG44 and U251 cell lines, so as to evaluate impacts of CCAT2 and miR-424 on chemosensitivity of the glioma cells. Besides, proliferation, invasion and metastasis of the cells were determined through the implementation of colony formation assay, transwell assay and scratch assay. Results Glioma tissues and cells were monitored with higher CCAT2 expression and lower miR-424 expression than adjacent normal tissues and NHA cell line (P<0.05). Among the glioma cell lines, the SHG44 cell line showed the strongest resistance against teniposide, temozolomide and cisplatin (P<0.05), whereas the U251 cell line was more sensitive to teniposide, temozolomide, vincristine and cisplatin than any other cell line (P<0.05). Besides, pcDNA3.1-CCAT2 and miR-424 inhibitor could enhance tolerance of glioma cell lines against drugs (P<0.05). Moreover, in-vitro transfection of si-CCAT2 and miR-424 mimic could significantly retard proliferation, invasion and migration of SHG44 and U251 cells (P<0.05), and CCAT2 was found to negatively regulate miR-424 expression by sponging it (P<0.05). In addition, CHK1 was deemed as the molecule targeted by upstream miR-424, and its overexpression can changeover the effects of miR-424 mimic on proliferation and metastasis of SHG44 and U251 cells. Conclusion lncRNA CCAT2/miR-424/Chk1 axis might serve as a promising target for improving chemotherapeutic efficacies in glioma treatment.
Collapse
Affiliation(s)
- Jun Ding
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China
| | - Lin Zhang
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China
| | - Shiwen Chen
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China
| | - Heli Cao
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China
| | - Chen Xu
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China
| | - Xuyang Wang
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China
| |
Collapse
|
|
2
|
Fang J, Huang J. Clinical significance of the expression of long non-coding RNA PVT1 in glioma. Cancer Biomark 2019; 24:509-513. [PMID: 30909189 DOI: 10.3233/cbm-182253] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Glioma is the most common primary malignant tumor in the nervous system. OBJECTIVE To investigate the expression of long non-coding RNA Pvt1 oncogene (PVT1) in glioma and its clinical significance. METHODS The expression levels of PVT1 were determined in 59 glioma and 10 normal tissue samples using qRT-PCR. The patients were divided into high and low expression groups and analyzed for their relationship with clinicopathological factors and the survival time using the Kaplan-Meier method. RESULTS The expression levels of PVT1 were significantly higher in glioma tissues than in normal tissues (p< 0.01) and higher in high grade (III-IV) than in low grade (I-II) tumors (p< 0.01). Analysis showed that the PVT1 level was closely related to glioma grade (p< 0.01), but not to age, gender, Karnofsky performance status (KPS) and tumor size (p> 0.05). Receiver operator characteristic curve analysis showed an area under the curve of 0.835. Log-rank test showed that the prognosis of high PVT1 group was poorer than that of low PVT1 group (p< 0.01). CONCLUSIONS PVT1 is highly expressed in gliomas and its level is positively related to WHO glioma grade and prognosis of gliomas. Therefore, it may be explored as a new molecular marker for predicting malignancy and prognosis of gliomas.
Collapse
|
|
3
|
Liu H, Mao P, Xie C, Xie W, Wang M, Jiang H. Association between interleukin 8-251 T/A and +781 C/T polymorphisms and glioma risk. Diagn Pathol 2015; 10:138. [PMID: 26249370 PMCID: PMC4528780 DOI: 10.1186/s13000-015-0378-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Accepted: 07/29/2015] [Indexed: 01/16/2023] Open
Abstract
Background Gliomas are aggressive tumors of the central nervous system that rely on production of growth factors for tumor progression. Interleukin 8 (IL-8) is up-regulated in gliomas to promote angiogenesis and proliferation. The aim of this study was to evaluate the association of the IL-8 -251 T/A and +781 C/T polymorphisms and glioma risk. Methods We enrolled 300 glioma patients and 300 age- and gender-matched healthy controls. A prospective hospital-based case–control design and logistic regression analysis were utilized. The IL-8 gene polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Glioma patients had a significantly higher frequency of IL-8 -251 AA genotype [odds ratio (OR) =1.91, 95 % confidence interval (CI) = 1.22, 3.00; P = 0.005] and IL-8 -251 A allele (OR =1.36, 95 % CI = 1.08, 1.70; P = 0.009) than controls. When stratified by the grade of glioma, patients with WHO IV glioma had a significantly higher frequency of IL-8 -251 AA genotype (OR =1.56, 95 % CI = 1.01, 2.39; P = 0.04). Conclusions To the best of our knowledge, this is the first report in the literature that the IL-8 -251 AA genotype and A allele were at a higher risk for glioma.
Collapse
Affiliation(s)
- Hao Liu
- Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiao Tong University, West Yanta Road No.277, Xi'an, 710061, China.
| | - Ping Mao
- Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiao Tong University, West Yanta Road No.277, Xi'an, 710061, China.
| | - Changhou Xie
- Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiao Tong University, West Yanta Road No.277, Xi'an, 710061, China.
| | - Wanfu Xie
- Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiao Tong University, West Yanta Road No.277, Xi'an, 710061, China.
| | - Maode Wang
- Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiao Tong University, West Yanta Road No.277, Xi'an, 710061, China.
| | - Haitao Jiang
- Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiao Tong University, West Yanta Road No.277, Xi'an, 710061, China.
| |
Collapse
|
|
4
|
X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism significantly associated with prostate cancer. Int J Biol Markers 2015; 30:e12-21. [PMID: 25262700 DOI: 10.5301/jbm.5000111] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/10/2014] [Indexed: 12/20/2022]
Abstract
Prostate cancer (Pca) is one of the noncutaneous cancers occurring worldwide. Its high morbidity and mortality make it a concern. X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism (rs25487) has been reported to be related to Pca. However, the conclusions are controversial. In this study, PubMed, HuGENet and Chinese National Knowledge Infrastructure (CNKI) databases were combined with a comprehensive literature search. Four models including dominant (AA + AG vs. GG), recessive (AA vs. AG+GG), codominant (AA vs. AG, AA vs. GG) and per-allele analysis (A vs. G) were applied. Finally, 15 studies with 18 sets of data were included. A positive association was discovered in pooled results for recessive (odds ratio [OR]=1.202, 95% confidence interval [95% CI], 1.060-1.363, I2=46.20%), codominant (AA vs. AG; OR=1.258, 95% CI, 1.099-1.439, I2=38.50%; AA vs. GG; OR=1.283, 95% CI, 1.027-1.602, I2=51.70%) and allele analysis (OR=1.116, 95% CI, 1.001-1.244, I2=58.00%). In ethnicity subgroup analysis, these 4 models were also significant in the Asian subgroup. However, for whites, only 2 models seemed to be significant (AA vs. AG+GG: OR=1.525, 95% CI, 1.111-2.093, I2=52.60%; AA vs. AG: OR=1.678, 95% CI, 1.185-2.375, I2=30.70%). In further analysis, we regrouped the data based on race, in which pooled results and Asian subgroup were again shown to be positive. In the next analysis, expression quantitative trait loci (eQTL), linkage disequilibrium (LD), TagSNP and functional analysis were used. The results showed that the SNP was a tag and functional SNP with LD block in both Asians and whites. In summary, we suggest that XRCC1 Arg399Gln might be significantly associated with development of Pca.
Collapse
|
|
5
|
Ma QY, Chen J, Wang SH, Wu N, Hao ZH, Chen XF. Interleukin 17A genetic variations and susceptibility to non-small cell lung cancer. APMIS 2014; 123:194-8. [PMID: 25469655 DOI: 10.1111/apm.12341] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2014] [Accepted: 09/25/2014] [Indexed: 12/15/2022]
Abstract
Lung cancer is the leading cause of cancer-related death, in which non-small cell lung cancer (NSCLC) is the most common type. Evidence have shown that interleukin 17 (IL-17) greatly involves in human immune responses. In this study, we investigated the effect of IL-17 on NSCLC by examining the association between IL-17A genetic polymorphisms and the susceptibility to NSCLC. IL-17A -420A/G and IL-17A -73G/A polymorphisms were detected in 330 NSCLC patients and 382 healthy controls. We found that subjects carrying -73GA genotype or AA genotype had 2.09-fold or 2.52-fold increased risk of NSCLC than those with -73GG genotype [odds ratio (OR) = 2.09, 95% confidence interval (CI), 1.46 - 2.98, p < 0.001; OR = 2.52, 95% CI, 1.30-4.88, p = 0.005, respectively). However, the IL-17A -420A/G did not reveal any correlation with the cancer. Further investigation showed that prevalence of IL-17A -73GA genotype and A allele were significantly increased in adenocarcinoma patients (OR = 1.75, 95% CI, 1.08-2.86, p = 0.024, OR = 1.57, 95% CI, 1.09-2.28, p = 0.016, respectively). We also evaluated the effect of the polymorphisms on gene expression, and identified that peripheral blood mononuclear cells with IL-17A -73GA and AA genotypes produced significantly higher level of IL-17 than the cells with IL-17A -73GG genotype. Our results suggest that IL-17A -73G/A genetic variations may upregulate IL-17 expression and are associated with increased susceptibility to NSCLC.
Collapse
Affiliation(s)
- Qin-Yun Ma
- Department of Thoracic Surgery, Huashan Hospital Affiliated to Fudan University, Shanghai, China
| | | | | | | | | | | |
Collapse
|
|
6
|
He LW, Shi R, Jiang L, Zeng Y, Ma WL, Zhou JY. XRCC1 gene polymorphisms and glioma risk in Chinese population: a meta-analysis. PLoS One 2014; 9:e111981. [PMID: 25375625 PMCID: PMC4222958 DOI: 10.1371/journal.pone.0111981] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2014] [Accepted: 10/03/2014] [Indexed: 01/18/2023] Open
Abstract
Background Three extensively investigated polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) in the X-ray repair cross-complementing group 1 (XRCC1) gene have been implicated in risk for glioma. However, the results from different studies remain inconsistent. To clarify these conflicts, we performed a quantitative synthesis of the evidence to elucidate these associations in the Chinese population. Methods Data were extracted from PubMed and EMBASE, with the last search up to August 21, 2014. Meta-analysis was performed by critically reviewing 8 studies for Arg399Gln (3062 cases and 3362 controls), 8 studies for Arg194Trp (3419 cases and 3680 controls), and 5 studies for Arg280His (2234 cases and 2380 controls). All of the statistical analyses were performed using the software program, STATA (version 11.0). Results Our analysis suggested that both Arg399Gln and Arg194Trp polymorphisms were significantly associated with increased risk of glioma (for Arg399Gln polymorphism: Gln/Gln vs. Arg/Arg, OR = 1.82, 95% CI = 1.46–2.27, P = 0.000; Arg/Gln vs. Arg/Arg, OR = 1.25, 95% CI = 1.10–1.42, P = 0.001 and for Arg194Trp polymorphism: recessive model, OR = 1.78, 95% CI = 1.44–2.19, P = 0.000), whereas the Arg280His polymorphism had no influence on the susceptibility to glioma in a Chinese population. Conclusions This meta-analysis suggests that there may be no association between the Arg280His polymorphism and glioma risk, whereas the Arg399Gln/Arg194Trp polymorphisms may contribute to genetic susceptibility to glioma in the Chinese population. Nevertheless, large-scale, well-designed and population-based studies are needed to further evaluate gene-gene and gene–environment interactions, as well as to measure the combined effects of these XRCC1 variants on glioma risk.
Collapse
Affiliation(s)
- Li-Wen He
- Institute of Genetic Engineering, Southern Medical University, Guangzhou, China
- Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Rong Shi
- Institute of Genetic Engineering, Southern Medical University, Guangzhou, China
| | - Lei Jiang
- Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Ye Zeng
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Wen-Li Ma
- Institute of Genetic Engineering, Southern Medical University, Guangzhou, China
| | - Jue-Yu Zhou
- Institute of Genetic Engineering, Southern Medical University, Guangzhou, China
- * E-mail:
| |
Collapse
|
|
7
|
Li J, Qu Q, Qu J, Luo WM, Wang SY, He YZ, Luo QS, Xu YX, Wang YF. Association between XRCC1 polymorphisms and glioma risk among Chinese population. Med Oncol 2014; 31:186. [PMID: 25245010 DOI: 10.1007/s12032-014-0186-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Accepted: 08/12/2014] [Indexed: 12/26/2022]
Abstract
The pathogenesis of glioma remains largely unknown now. It has been suggested that the X-ray cross-complementing group 1 (XRCC1) gene may influence the capacity to repair DNA damage leading to an increased gliomas susceptibility. This study aimed to evaluate the relationship between XRCC1 polymorphisms and glioma risk. Genotypes were assessed in 368 Chinese glioma patients and 346 healthy controls. XRCC1 Arg194Trp (rs1799782), Arg280His (rs25489) and Arg399Gln (rs25487) and three additional polymorphisms were directly sequenced. The frequency of Arg280His A allele was significant lower in glioma group than in healthy controls [9.6 vs 16%, OR=0.60 (0.46-0.80), P<0.001]; the frequencies of GA or AA genotypes were different in two groups (16.6 vs 22.8%, 1.3 vs 4.7%). The frequency of Arg399Gln A allele was significant higher in glioma group than in healthy controls [38.7 vs 30.1%, OR=1.29 (1.11-1.49), P=0.001]; the frequencies of GA or AA genotypes were different in two groups (45.4 vs 38.2%, 16 vs 10.9%). This study demonstrates that the rs25489 (Arg280His) and Arg399Gln (rs25487) polymorphisms in XRCC1 gene might influence the risk of developing glioma in Chinese population.
Collapse
Affiliation(s)
- Jiang Li
- Department of Clinical Laboratory, Hunan Provincial People's Hospital, Changsha, 410005, People's Republic of China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
8
|
Zhou JY, Shi R, Jiang L, Zeng Y, Ma WL. Letter regarding Zhu et al. entitled "Assessment of the association between XRCC1 Arg399Gln polymorphism and glioma susceptibility". Tumour Biol 2014; 35:6181-2. [PMID: 24715306 DOI: 10.1007/s13277-014-1931-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2014] [Accepted: 04/03/2014] [Indexed: 10/25/2022] Open
Affiliation(s)
- Jue-Yu Zhou
- Institute of Genetic Engineering, Southern Medical University, 1838 North Guangzhou Avenue, 510515, Guangzhou, China,
| | | | | | | | | |
Collapse
|