1.KRT14 promotes the invasion and migration of basal-like breast cancer through activating the Wnt/β-catenin pathway
Zheng Cheng ; Manman Zhang ; Jingni Zhou ; Qianying Guo ; Zhengsheng Wu
Acta Universitatis Medicinalis Anhui 2025;60(5):805-815
Objective :
To investigate the expression of Keratin 14(KRT14) in Basal-like Breast Cancer(BLBC) and its biological functions and mechanisms.
Methods :
The expression levels of KRT14 mRNA in BLBC and para-cancer breast tissues were analyzed using The Cancer Genome Atlas(TCGA) database. qPCR, Western blot(WB), and immunohistochemistry were employed to detect KRT14 expression in BLBC and adjacent normal tissues, and its correlation with clinicopathological features was analyzed. KRT14 overexpression and knockdown were performed in breast cancer cells, and cell scratch and transwell assays were performed to evaluate changes in migration and invasion abilities. To investigate the expression of proteins related to the Wnt/β-catenin signaling pathway, including catenin Beta 1(β-catenin), wingless-type MMTV integration site family, member 1(Wnt1), matrix metallopeptidase 7(MMP7), and cellular myelocytomatosis viral oncogene homolog(c-Myc), as well as the cellular localization of β-catenin, WB and immunofluorescence(IF) techniques were employed. Additionally, a Wnt/β-catenin signaling pathway inhibitor was used to verify the mechanism of action of KRT14.
Results :
The expression of KRT14 was significantly higher in BLBC tissues compared to normal tissues(P<0.05), and was associated with higher T stage and histological grade(P<0.05). The overexpression of KRT14 significantly enhanced the migration and invasion abilities of breast cancer cells, while the knockdown of KRT14 significantly reduced those abilities(P<0.01). The overexpression of KRT14 can increase the expression levels of Wnt/β-catenin pathway-related proteins β-catenin, Wnt1, MMP7, and c-Myc, thereby activating the Wnt/β-catenin pathway. Moreover, the inhibition of this pathway can eliminate the effects of KRT14 on cell migration and invasion.
Conclusion
The high expression of KRT14 in BLBC may promote the migration and invasion of breast cancer cells through the Wnt/β-catenin signaling pathway.
2.Expression of HSPA8 in breast cancer and its biological function
Manman Zhang ; Zheng Cheng ; Jingni Zhou ; Qianying Guo ; Zhengsheng Wu
Acta Universitatis Medicinalis Anhui 2025;60(5):816-825
Objective :
To investigate the expression of(heat shock protein a member 8,HSPA8) in breast cancer and its effect on tumor biological behaviors.
Methods:
Bioinformatics analysis and immunohistochemistry assays were used to detect the expression of HSPA8 in breast cancer and adjacent non-tumor breast tissues,and the relationship between its expression and clinicopathological characteristics of breast cancer patients was analyzed.Correlation between HSPA8 expression and prognosis of breast cancer patients was analyzed by Kaplan-Meier Plotter database.HSPA8 knockdown and over expression breast cancer stabilized cells were constructed,respectively.CCK-8,clone formation,Transwell,cell scratch,Western blot and immunofluorescence assay were used to detect the effects of HSPA8 on the proliferation,invasion and migration of breast cancer cells,and its effect on epithelial-mesenchymal transition(EMT).
Results :
Bioinformatics analysis and immunohistochemistry assay revealed that the expression of HSPA8 in breast cancer tissues was higher than that in adjacent non-tumour tissues(P<0.05),and its expression level of the protein was significantly and positively correlated with the tumor size,histological grade,lymph node metastasis and Ki-67 proliferation index(P<0.05).The Kaplan-Meier survival curve showed that high expression of HSPA8 was significantly associated with poor prognosis in breast cancer patients(P<0.05).CCK-8,clone formation,transwell,cell scratch,Western blot and immunofluorescence assay showed that knockdown of HSPA8 expression could significantly inhibit the proliferation,invasion,migration function and EMT of breast cancer cells(P<0.05),while overexpression of HSPA8 could significantly promote the proliferation,invasion,migration function and EMT of breast cancer cells(P<0.05).
Conclusion
HSPA8 is highly expressed in breast cancer tissues,which is closely related to disease progression and the malignant phenotype of breast cancer,suggesting that HSPA8 may be a potential biological target for breast cancer treatment.
3.Practice and exploration of new media health science popularization in university affiliated hospitals based on the interdisciplinary cooperation model of medical and cultural affairs
Dongqing LI ; Dongyan ZHANG ; Jiahui LIU ; Jingni WANG ; Jianjun ZHANG ; Xuan SU ; Jie LIU ; Jia YAO ; Jun YAN
Modern Hospital 2024;24(5):790-792
Public hospitals bear the responsibility of ensuring people's health and promoting their healthy lives.New media have emerged as a pivotal platform for health science popularization in public hospitals.Under these contexts,the Science Popularization Base for Health and Chronic Disease Prevention of the First Hospital of Lanzhou University established a multidisci-plinary team model for science popularization,mainly relying on the WeChat official account to disseminate health knowledge and dispel rumors.This article explored the experiences and practices of health science popularization under this model,focusing on the"meticulous selection for science popularization"strategy employed on their WeChat official account.
4.TBX1 inhibits the activation of MAPK and PI3K signaling pathway and reduces the proliferation of colorectal cancer cells thorough activating PARK2
Jingni ZHANG ; Tong HUANG ; Mengge BAI ; Jianling WANG ; Man ZHAO
Cancer Research and Clinic 2024;36(11):808-816
Objective:To investigate the effect of the transcription factor TBX1 on the proliferation of colorectal cancer cells and to explore potential molecular mechanisms.Methods:The mRNA and protein levels of TBX1 in colorectal cancer cell lines HCT116, RKO, SW480, HT29, and LOVO were detected by using reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Colorectal cancer cell lines HCT116 and SW480 cells with low TBX1 expression were transfected with either a pcDNA3.1 plasmid containing TBX1 mimics (TBX1 overexpression group) or an empty pcDNA3.1 plasmid (the control group). LOVO cells with high TBX1 expression were transfected with small interfering RNA (siRNA) targeting TBX1 including si-TBX1-8604A, si-TBX1-8604B, and a negative control siRNA (si-NC), which were treated as si-TBX1-8604A group, si-TBX1-8604B group, and si-NC group. qRT-PCR was used to detect the expressions of transcriptional level TBX1 and PARK2, and Western blot was used to detect the protein levels of TBX1, PARK2, and key factors in the MAPK and PI3K signaling pathways. Methyl Thiazolyl Tetrazolium (MTT) assay and cell colony formation assay were used to detect the cell proliferation. Combining literatures and the JASPAR database, 2 binding sites of TBX1 in the PARK2 promoter region were predicted. Chromatin immunoprecipitation assay was employed to verify the binding sites of TBX1 to PARK2 in HCT116 and SW480 cells. Dual luciferase reporter gene assay was used to verify the targeting relationship between TBX1 and PARK2. The expression of TBX1 and PARK2 in colon cancer tissues was analyzed by using the Cancer Genome Atlas (TCGA) database (September 2023).Results:High TBX1 expression in HCT116 and SW480 cells transfected with TBX1 mimics plasmid was confirmed by qRT-PCR and Western blot, while TBX1 expression was successfully knocked down in LOVO cells transfected with siRNA targeting TBX1. MTT assay indicated that the absorbance values for HCT116 cells in TBX1 overexpression group on d1, d3, d5, and d7 after inoculation, and for SW480 cells on d3, d5, and d7 after inoculation were lower than those in the control group, and the differences were statistically significant (all P < 0.01). LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group exhibited higher absorbance values than the si-NC group on d1, d3, d5, and d7 after inoculation, and the differences were statistically significant (all P < 0.05). Cell colony formation assay revealed that after 14 d, the colony number of HCT116 cells [(387±9) vs. (843±13)] and SW480 cells [(413±9) vs. (931±15)] in TBX1 overexpression group was lower than that in the control group, and the differences were statistically significant (all P < 0.05). The colony number of LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group was (493±77) and (470±32), respectively, which was higher than that in the si-NC group (349±26), and the differences were statistically significant (all P < 0.05). The protein relative expression levels of p-ERK and p-AKT S473 in HCT116 and SW480 cells in TBX1 overexpression group were lower than those in the control group, while protein relative expression levels of p-ERK and p-AKT S473 in LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group were higher than those in the si-NC group, and the differences were statistically significant (all P < 0.05). The relative expression level of PARK2 mRNA in HCT116 and SW480 cells (all P < 0.01) and the protein level in the overexpression group were higher than those in the control group. Chromatin immunoprecipitation assay demonstrated that the enrichment times of TBX1 binding to 2 sites of PARK2 intron in HCT116 and SW480 cells in TBX1 overexpression group were higher than that in the control group, and the differences were statistically significant (all P < 0.05). Dual luciferase reporter gene assay showed that the relative luciferase activity of HCT116 and SW480 cells co-transfected with pcDNA3.1 plasmid containing TBX1 mimics and pGL3 plasmid containing PARK2 mimics was higher than that of cells co-transfected with empty pcDNA3.1 and pGL3 plasmids, co-transfected with empty pcDNA3.1 plasmid and pGL3 plasmid containing PARK2 mimics, co-transfected with pcDNA3.1 plasmid containing TBX1 mimics and empty pGL3 plasmid, and the differences were statistically significant (all P < 0.05). Spearman analysis showed that there was a positive correlation between transcriptional level TBX1 and PARK2 in colon cancer tissues (288 cases) in TCGA database ( r = 0.226, P < 0.001); and the relative expression level of PARK2 mRNA in colon cancer tissues (383 cases) was lower than that in normal intestinal tissues (50 cases), and the difference was statistically significant ( P < 0.001). Conclusions:Elevated expression of transcriptional factor TBX1 inhibits the proliferation of colorectal cancer cells, potentially by activating the downstream target gene PARK2 and inhibiting the phosphorylation of ERK and AKT in the MAPK and PI3K signaling pathways, ultimately affecting the activation of these pathways.
5.Effects of individual or combination medication of epidermal growth factor receptor tyrosine kinase inhibitor combined with chemotherapy on progression-free survival in advanced non-small cell lung cancer patients with epidermal growth factor receptor mutation
Qingling GAO ; Yan CHANG ; Jingni WANG ; Jing ZHANG ; Qingke SUN
Journal of Clinical Medicine in Practice 2023;27(24):1-6
Objective To explore the effects of individual or combination medication of epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)combined with chemotherapy on progres-sion-free survival(PFS)in advanced non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutation.Methods A total of 110 advanced NSCLC patients with EGFR mutation in our hospital from January 2019 to April 2021 were selected as research objects.Ac-cording to different therapeutic plans,they were divided into group A with 37 cases(anlotinib chemo-therapy),group B with 32 cases(icotinib chemotherapy)and group C with 41 cases(anlotinib plus icotinib and chemotherapy).The short-term effect,levels of vascular growth factors before and after treatment,and the incidence of adverse reactions were compared among the three groups.After 2 years of follow-up,survival curve was drawn by Kaplan-Meier method,and survival rate and PFS were compared in three groups by Log-rank.Results The objective response rate(ORR)was 68.29%in the group C,which was significantly higher than 43.24%in the group A and 40.62%in the group B(P<0.05);after treatment,levels of serum vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF)and platelet-derived growth factor(PDGF)in the group C were significantly lower than those in the group A and the group B(P<0.05);the total incidence of adverse reac-tions was 29.27%in the group C,which showed no significant differences when compared to 24.32%in the group A and 25.00%in the group B(P>0.05).By the time of the last follow-up,the 2-year overall survival rate was 74.29%in the group C,which was significantly higher than 51.09%in the group A and 45.03%in the group B(Log-rank x2=6.478,P=0.039);the medi-an PFS in the group A,the group B and the group C was 9.0,8.6 and 13.2 months respectively,and differences were statistically significant(Log-rank x2=6.264,P=0.043).Conclusion For the advanced NSCLC patients with EGFR mutations,combination medication of EGFR-TKI com-bined with chemotherapy can effectively increase ORR,reduce levels of serum vascular growth fac-tors,prolong the PFS,and the safety is good.
6.Effects of individual or combination medication of epidermal growth factor receptor tyrosine kinase inhibitor combined with chemotherapy on progression-free survival in advanced non-small cell lung cancer patients with epidermal growth factor receptor mutation
Qingling GAO ; Yan CHANG ; Jingni WANG ; Jing ZHANG ; Qingke SUN
Journal of Clinical Medicine in Practice 2023;27(24):1-6
Objective To explore the effects of individual or combination medication of epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)combined with chemotherapy on progres-sion-free survival(PFS)in advanced non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutation.Methods A total of 110 advanced NSCLC patients with EGFR mutation in our hospital from January 2019 to April 2021 were selected as research objects.Ac-cording to different therapeutic plans,they were divided into group A with 37 cases(anlotinib chemo-therapy),group B with 32 cases(icotinib chemotherapy)and group C with 41 cases(anlotinib plus icotinib and chemotherapy).The short-term effect,levels of vascular growth factors before and after treatment,and the incidence of adverse reactions were compared among the three groups.After 2 years of follow-up,survival curve was drawn by Kaplan-Meier method,and survival rate and PFS were compared in three groups by Log-rank.Results The objective response rate(ORR)was 68.29%in the group C,which was significantly higher than 43.24%in the group A and 40.62%in the group B(P<0.05);after treatment,levels of serum vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF)and platelet-derived growth factor(PDGF)in the group C were significantly lower than those in the group A and the group B(P<0.05);the total incidence of adverse reac-tions was 29.27%in the group C,which showed no significant differences when compared to 24.32%in the group A and 25.00%in the group B(P>0.05).By the time of the last follow-up,the 2-year overall survival rate was 74.29%in the group C,which was significantly higher than 51.09%in the group A and 45.03%in the group B(Log-rank x2=6.478,P=0.039);the medi-an PFS in the group A,the group B and the group C was 9.0,8.6 and 13.2 months respectively,and differences were statistically significant(Log-rank x2=6.264,P=0.043).Conclusion For the advanced NSCLC patients with EGFR mutations,combination medication of EGFR-TKI com-bined with chemotherapy can effectively increase ORR,reduce levels of serum vascular growth fac-tors,prolong the PFS,and the safety is good.
7.Clinical efficacy of vascular rehabilitation capsules combined with calcium dobesilate on non-proliferative diabetic retinopathy and its effect on inflammatory factors
Shaolin PENG ; Siyu YU ; Shuibing YANG ; Juedi LI ; Jingni XIONG ; Meibiao ZHANG
Journal of Chinese Physician 2021;23(11):1651-1654,1659
Objective:To investigate the clinical efficacy of vascular rehabilitation capsules and calcium dobesilate on non-proliferative diabetic retinopathy and its effect on inflammatory factors.Methods:A total of 80 patients with type 2 diabetes and non-proliferative retinopathy diagnosed in the endocrinology department of First People′s Hospital of Huaihua were randomly divided into the control group ( n=40 cases, 72 eyes) and the observation group ( n=40 cases, 76 eyes). The two groups were given conventional basic treatment. The control group was given calcium dobesilate, and the observation group was added with the combination of vascular rehabilitation capsules and treatment for 24 weeks. After treatment, the clinical therapeutic effects of the two groups were evaluated, and the levels of inflammatory factors interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) were analyzed before and after treatment. The occurrence of adverse reactions was monitored during treatment. Results:The total effective rate of the observation group was higher than that of the control group (92.5% vs 75.0%, χ 2=4.501, P<0.05). There was no significant difference in the levels of IL-6 and hs-CRP in the two groups of patients before treatment [(4.41±0.92)pg/ml vs (4.47±0.84)pg/ml, (16.36±4.02)mg/L vs (16.38±3.26)mg/L]; after 12 weeks and 24 weeks of treatment, the levels of IL-6 and hs-CRP in the observation group were significantly lower than those in the control group [12 h: (2.55±0.64)pg/ml vs (2.94±0.59)pg/ml, (12.21±3.48)mg/L vs (14.33±3.04)mg/L; 24 h: (1.93±0.49)pg/ml vs (2.36±0.45)pg/ml, (9.63±3.05)mg/L vs (11.52±2.15)mg/L, all P<0.05]. During the treatment, no serious adverse events occurred in both groups of patients. Conclusions:Vascular rehabilitation capsules combined with calcium dobesilate is an effective treatment for non proliferative diabetic retinopathy. It can improve the clinical efficacy, safety and reduce inflammatory reaction, which is worthy of further clinical application.
8.Research advances in TET enzyme and its intermediate product 5hmC.
Jingni WU ; Xiaoling FANG ; Xiaomeng XIA ; Mengmeng ZHANG
Journal of Central South University(Medical Sciences) 2019;44(4):449-454
DNA methylation is a significant epigenetic modification mode, which plays an important role in embryo reprogramming, stem cell differentiation and tumor occurrence. The ten-eleven translocation (TET) enzyme is a crucial demethylation enzyme, which can catalyze 5-methylcytosine(5mC) to 5-hydroxymethylcytosine(5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine(5caC). These bases represent the epigenetic modifications of DNA and regulate the process of DNA methylation. Understanding the role of TET enzyme in regulating the DNA methylation modification and gene expression can help us to gain the knowledge for the normal growth development and epigenetic regulation in human diseases.
5-Methylcytosine
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metabolism
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Cell Differentiation
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DNA
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DNA Methylation
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DNA-Binding Proteins
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Epigenesis, Genetic
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Humans
9.Epidemic status of alveolar echinococcosis in Tibetan children in south Qing-hai Province
Xiumin HAN ; Xueyong ZHANG ; Qigang CAI ; Jingni ZHANG ; Yongshun WANG ; Qiang ZHANG
Chinese Journal of Schistosomiasis Control 2017;29(1):53-58
Objective To understand the epidemic status of alveolar echinococcosis in Tibetan children in south Qinghai Province. Methods The imageology and serology methods were applied to investigate the epidemic status of alveolar echinococ?cosis of elementary school students in Yushu and Guoluo prefectures. Results Totally 19 629 children were investigated by the portable B ultrasound and 221 children were diagnosed as alveolar echinococcosis with the morbidity of 1.13%. Totally 9 888 were investigated by the indirect ELISA,and the positive rate of serum tests was 12.59%(190/9 888). The total morbidity of al?veolar echinococcosis of children in Yushu Prefecture was 0.42%(31/7 454)and it was 1.57%(190/12 175)in Guoluo Prefec?ture and there was a significant difference between them(χ2=53.42,P<0.005). The sero?positive rates of children in Yushu and Guoluo were 4.26%(302/7 081)and 18.56%(1 835/9 888),respectively(χ2 =765.77,P<0.005). The counties with the highest prevalence of alveolar echinococcosis in children were Dari County (4.31%,106/2 461) and Banma County (1.92%,26/1 351)of Guoluo Prefecture ,and Chengduo County(1.11%,18/1 612)of Yushu Prefecture. The total morbid?ity rates of alveolar echinococcosis of male and female children were 0.91%(91/9 954)and 1.34%(130/12 175)respective?ly(χ2=7.35,P<0.005). The total sero?positive rates of alveolar echinococcosis of male and female children were 12.10%(1 037/8 568)and 13.09%(1 100/8 406)respectively(χ2=3.63,P>0.05). The total morbidity of alveolar echinococcosis of children in different age groups was from 1.00%to 1.13%,and there was no significant difference among the age groups(χ2=2.73,P>0.05). The P1a type,P1b type and P2 type accounted for 67.76%(145/214),10.75%(23/214)and 16.36%(35/214)respectively among the alveolar echinococcosis patients. The diameters of nidus of 87.38%(187/214)patients were less than 5 cm,and 2.80%(6/214)were more than 10 cm. Conclusions The epidemic status of alveolar echinococcosis of Tibetan children in south Qinghai Province is serious,but most of the patients were at early stage of the disease. The screening work of al?veolar echinococcosis should be strengthened in Tibetan children,so as to perform the early diagnosis and treatment.
10.Influencing factors of prevention and control knowledge of echinococcosis in people in Qinghai Province
Jingni ZHANG ; Xiumin HAN ; Yaping WANG ; Wen LEI ; Yongshun WANG ; Wei WANG
Chinese Journal of Endemiology 2017;36(12):907-911
Objective To understand the situation of prevention and control knowledge of echinococcosis in people,and analyze the influencing factors of prevention and control knowledge of echinococcosis,so as to provide efficient and targeted evidence for taking intervention measures against echinococcosis.Methods All the districts (counties) in agricultural and pastoral area-based cities (zhous) in Qinghai Province were selected,3 townships were selected in each district (county),and 100 residents were randomly selected in each township via the stratified random sampling method.In each district (county),students of Grade Four or higher were randomly selected via the multi-stage stratified cluster sampling method,they were all investigated through a questionnaire survey about echinococcosis in Qinghai Province in 2012-2014.The influencing factors of prevention and control knowledge of echinococcosis were analyzed using Logistic regression analysis,including age,gender and district.Results Totally 11 959 residents and 23 600 students were selected and surveyed,and the qualified rate of residents and students in prevention and control knowledge of echinococcosis was 62.4% (7 464 cases) and 66.0%(15 566 cases),respectively,and the difference was statistically significant (x2 =43.695,P < 0.01).The aware rate of echinococcosis knowledge between residents and students was significantly different (x2 =113.680,60.712,1 204.943,273.296,P < 0.01) except the question "washing hands before eating".Logisitic regression analysis showed that the main factors influencing the qualified rate of echinococcosis of residents were age (OR =0.989,95%CI:0.986-0.991) and district (compared with Huangnan Zhou,Haidong City OR =3.478,95%CI:2.978-4.063;Haixi Zhou OR =10.284,95%CI:8.578-12.330;Hainan Zhou OR =7.750,95%CI:6.468-9.286;Haibei Zhou OR =11.056,95%CI:9.089-13.448;Guoluo Zhou OR =7.309,95%CI:6.132-8.713;and Yushu Zhou OR =0.319,95%CI:0.258-0.393);and the main factors influencing the qualified rate of echinococcosis of students were age (OR =0.981,95%CI:0.964-0.998),gender (OR =1.103,95%CI:1.040-1.170) and district (compared with Huangnan Zhou,Xi'ning City OR =5.428,95%CI:4.823-6.109;Haidong City OR =3.860,95%CI:3.437-4.334;Haixi Zhou OR =6.557,95%CI:5.750-7.477;Hainan Zhou OR =2.757,95%CI:2.444-3.112;Haibei Zhou OR =9.968,95%CI:8.498-11.692;Guoluo Zhou OR =4.306,95%CI:3.653-5.075;and Yushu Zhou OR =0.616,95%CI:0.545-0.695).Conclusions The general aware rate of echinococcosis knowledge in people is not high in Qinghai Province.The main factors that have influenced the qualified rate of echinococcosis knowledge of residents are age and district,and of students are age,gender and district.It is necessary to implement the targeted intervention measures to improve mastering level of prevention and control knowledge of echinococcosis of people in Qinghai Province.


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