1.ADAR1 Regulates the ERK/c-FOS/MMP-9 Pathway to Drive the Proliferation and Migration of Non-small Cell Lung Cancer Cells.
Li ZHANG ; Xue PAN ; Wenqing YAN ; Shuilian ZHANG ; Chiyu MA ; Chenpeng LI ; Kexin ZHU ; Nijia LI ; Zizhong YOU ; Xueying ZHONG ; Zhi XIE ; Zhiyi LV ; Weibang GUO ; Yu CHEN ; Danxia LU ; Xuchao ZHANG
Chinese Journal of Lung Cancer 2025;28(9):647-657
BACKGROUND:
Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration.
METHODS:
Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism.
RESULTS:
ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression.
CONCLUSIONS
High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans
;
Lung Neoplasms/physiopathology*
;
Adenosine Deaminase/genetics*
;
Matrix Metalloproteinase 9/genetics*
;
Cell Proliferation
;
Carcinoma, Non-Small-Cell Lung/physiopathology*
;
Cell Movement
;
Animals
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Mice
;
RNA-Binding Proteins/genetics*
;
Female
;
Male
;
Cell Line, Tumor
;
Proto-Oncogene Proteins c-fos/genetics*
;
Middle Aged
;
MAP Kinase Signaling System
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Gene Expression Regulation, Neoplastic
;
Mice, Nude
;
Extracellular Signal-Regulated MAP Kinases/genetics*
2.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
Objective:
To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value.
Methods:
A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL).
Results:
A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%).
Conclusion
The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.
3.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
Objective:
To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value.
Methods:
A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL).
Results:
A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%).
Conclusion
The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.
4.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
Objective:
To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value.
Methods:
A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL).
Results:
A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%).
Conclusion
The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.
5.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
Objective:
To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value.
Methods:
A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL).
Results:
A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%).
Conclusion
The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.
6.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
Objective:
To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value.
Methods:
A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL).
Results:
A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%).
Conclusion
The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.
7.Long-Term Exposure to Low-Level Ambient Air Pollution and Mortality among 0.3 Million Chinese Older Adults.
Likun LIU ; Xueli YUAN ; Wenqing NI ; Jing WEI ; Tingting LIU ; Ruijun XU ; Yingxin LI ; Zihua ZHONG ; Yi ZHENG ; Sihan LIANG ; Rui WANG ; Jian XU ; Yuewei LIU
Biomedical and Environmental Sciences 2024;37(12):1362-1372
OBJECTIVE:
Evidence that long-term exposure to ambient air pollution increases mortality among older adults, particularly those residing in low-level air pollution locations, remains scarce. This study investigated the potential links between long-term low-level air pollution exposure and mortality among Chinese older adults.
METHODS:
A population-based study with 317,464 individuals aged ≥ 65 years was conducted in Shenzhen, China during 2018 and 2020. Logistic regression models were used to analyze the associations between long-term exposure to air pollution and all-cause mortality, as the primary outcome, as well as non-accidental, cancer and cardiovascular mortality.
RESULTS:
Significant associations of PM 1, PM 2.5, PM 10, SO 2, CO, and O 3 exposures with a higher risk of all-cause mortality were found. Adjusted odds ratio ( OR) for each 1 µg/m 3 increment was 1.49 [95% confidence interval ( CI): 1.46, 1.53] for PM 1, 1.30 (1.27, 1.32) for PM 2.5, 1.05 (1.04, 1.06) for PM 10, 5.84 (5.39, 6.32) for SO 2, 1.04 (1.04, 1.05) for CO, and 1.02 (1.00, 1.03) for O 3, respectively. Long-term PM 1, PM 2.5, PM 10, SO 2, and CO exposures also elevated the risks of non-accidental, cancer and cardiovascular mortality.
CONCLUSION
Long-term low-level air pollution exposure was associated with an increased mortality risk among Chinese older adults.
Humans
;
Aged
;
China/epidemiology*
;
Male
;
Female
;
Air Pollution/adverse effects*
;
Environmental Exposure/adverse effects*
;
Air Pollutants/analysis*
;
Aged, 80 and over
;
Particulate Matter/adverse effects*
;
Cardiovascular Diseases/mortality*
;
Mortality
;
Neoplasms/mortality*
;
East Asian People
8.Analysis of the correlation between estrogen level and retinopathy in postmenopausal patients with type 2 diabetes
Huan LIAO ; Meilan YANG ; Wei ZUO ; Wen YAN ; Weiyong ZHANG ; Jia CHENG ; Wenqing ZHONG
Clinical Medicine of China 2018;34(3):263-267
Objective To investigate the correlation between postmenopausal estrogen levels and diabetic retinopathy in patients with type 2 diabetes.Methods Two hundred cases of postmenopausal type 2 diabetes admitted to the Eighth Affiliated Hospital,Sun Yat-sen University from January 2015 to January 2017 were selected as the subjects and divided into the retinopathy group (93 cases) and the normal retina group (107 cases) according to the resuhs of fundus angiography.The general data of the two groups were compared,and the blood glucose index,blood lipid index and estrogen level were measured and compared.Logistic regression analysis was used to analyze the related factors of the patients with retinopathy.Results (1) The disease duration of patients in the retinopathy group was longer than that in the normal retina group ((14.67 ±3.48) years vs.(10.20±2.85) years;t=9.983,P<0.05).The fasting blood glucose (FBG),glycosylated hemoglobin of patients in the retinopathy group were higher than those in the normal retina group (FBG:(8.01 ± 1.21) mmol/L vs.(6.93 ± 1.20) mmol/L,FBG:(8.32 ± 1.56) mmol/L vs.(7.39 ± 1.43) mmol/L;t =6.324,4.397,P<0.05).The total cholesterol (TC),triglyceride (TG) and low density lipoprotein (LDL-C) of patients in the retinopathy group were higher than those in the normal retina group [TC:(4.93±0.87) mmol/ Lvs.(4.23± 0.69) mmol/L,TG:(1.91 ± 0.42) mmol/L vs.(1.63 ± 0.32) mmol/L,LDL-C:(2.61 ± 0.90) mmol/L vs.(1.78±0.53) mmol/L;t =6.340,5.340,8.067,P<0.05],while high density lipoprotein (HDL-C) was lower than that in the normal retina group ((1.23±0.37) mmol/L vs.(1.76±0.45) mmol/L;t =9.014,P <0.05).The E2 level in the retinopathy group was lower than that in the normal retina group ((23.91 + 8.51) ng/L vs.(32.18 + 9.80) ng/L;t=6.325,P<0.05).Logistic regression analysis showed that the duration of diabetes,FBG,HbAlc,TC,TG and LDL-C were risk factors of retinopathy (OR (95% CI) =1.049 (1.011 ~ 1.056),1.071(1.061 ~ 1.093),1.092(0.984~ 1.275),1.099(1.661 ~ 1.993),1.863(1.661 ~ 1.993),1.652 (1.461 ~ 1.893),P< 0.05),while HDL-C and E2 were protective factors of retinopathy (OR (95 % CI) =0.172(0.061 ~ 0.293),0.955 (0.861 ~ 1.093),P<0.0S).Conclusion Estrogen level is related to retinopathy in postmenopausal diabetic patients.It may be a protective factor for diabetic retinopathy.
10.Twist regulation of EMT and its clinical significance in monitoring circulating tumor cells and evaluating effects of anticancer drugs
Wenqing LI ; Yi DING ; Yu JIANG ; Zhong LU ; Lihua WANG
Chinese Journal of Clinical Oncology 2016;43(17):770-774
Tumor cell plasticity, including epithelial to mesenchymal transition (EMT) and its reverse program, mesenchymal to epithe-lial transition (MET), regulates circulating tumor cells and carcinoma metastasis. Twist is overexpressed in rhabdomyosarcoma, breast cancer, gastric cancer, and other tumors. Twist, as a transcriptional factor, cross-talks with multiple signaling pathways, forming a com-plex network to participate in the regulation of EMT/MET in circulating tumor cells, which in turn promotes metastasis of tumor cells. Therefore, monitoring the level of Twist and epithelial–mesenchymal phenotypic molecules is important as it may be beneficial for in-creasing the detection ratio of circulating tumor cells as tumor biomarkers and for evaluating the effects of anticancer drugs.

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