1.LINC01503 promotes progression of epithelial ovarian cancer through the miR-342-3p/IGF2R axis
LYU Wei1a ; WANG Jiali1a ; LIU Tianxu1a ; DUAN Yuqing1a ; WANG Jun2 ; LIU Lihua1a,1b,1c
Chinese Journal of Cancer Biotherapy 2023;30(9):754-761
[摘 要] 目的:探讨LINC01503在上皮性卵巢癌(EOC)中的表达水平和生物学功能及其可能的作用机制。方法:收集2015年5月至2016年5月间在河北医科大学第四医院妇瘤科手术切除并经病理学确诊的85例EOC患者的肿瘤组织和输卵管组织。常规培养人EOC细胞A2780、SKOV3、OVCAR3和OV90及正常人卵巢上皮细胞IOSE80,将si-LINC01503、si-NC及miR-342-3p mimic、miR mimic NC分别转染至SKOV3和A2780细胞,分别作为si-LINC01503组、si-NC组、miR-342-3p mimic组和miR mimic NC组。qPCR法检测EOC组织和细胞中LINC01503的表达水平,Kaplan-Meier法分析LINC01503表达水平与患者生存的关系。双荧光素酶报告基因实验验证LINC01503/miR-342-3p/IGF2R轴相关分子间的靶向关系。平板克隆、划痕愈合和Transwell实验分别检测敲低LINC01503及转染miR-342-3p mimic对A2780和SKOV3细胞增殖、迁移和侵袭能力的影响。WB法检测EOC细胞中LINC01503/miR-342-3p通路对IGF2R蛋白表达的影响。构建A2780细胞裸鼠移植瘤模型,观察敲低LINC01503对移植瘤生长的影响。结果:EOC组织和细胞中LINC01503表达水平分别显著高于输卵管组织和IOSE80细胞(均P<0.01),LINC01503高表达组患者术后PFS和OS均显著短于LINC01503低表达组患者(均P<0.01)。敲低LINC01503、转染miR-342-3p mimic均可抑制EOC细胞的增殖、迁移和侵袭能力(均P<0.01)。敲低LINC01503可下调IGF2R的表达(P<0.01),这一现象可通过转染miR-342-3p inhibitor挽救。敲低LINC01503可抑制A2780细胞裸鼠移植瘤的生长(P<0.01)。结论:在EOC组织和细胞中呈高表达的LINC01503与患者的不良预后密切相关,LINC01503可能通过吸附miR-342-3p影响IGF2R表达进而促进EOC的进展。
3.Purple sweet potato anthocyanin regulates the proliferation, migration and invasion of breast cancer MDA-MB-231 cells through circ_0003998/miR-145 axis
MA Jianping ; SONG Lianchuan ; ZHAO Chengmao ; LYU Yong ; LI Hua ; WANG Xuechang
Chinese Journal of Cancer Biotherapy 2021;28(7):672-679
[摘 要] 目的:探讨紫甘薯花色苷(purple sweet potato anthocyanin, PSPA)是否通过circ_0003998/miR-145轴调控乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭。方法:选用乳腺癌MDA-MB-231细胞,将其分为对照组,200、400和800 μg/ml PSPA组,pcDNA组、pcDNA-circ_0003998组、si-NC组、si-circ_0003998组、si-circ_0003998+anti-miR-145组、PSPA+pcDNA组、PSPA+pcDNA-circ_0003998组和PSPA+anti-miR-145组。用qPCR法检测细胞中circ_0003998和miR-145的表达,CCK-8法、Transwell小室法分别检测转染前后细胞的增殖、迁移和侵袭能力,WB法检测细胞中Ki-67、MMP-2和MMP-9蛋白的表达。用双荧光素酶报告基因实验验证circ_0003998与miR-145的靶向关系。结果:与对照组比较,各剂量PSPA组MDA-MB-231细胞的增殖抑制率、miR-145表达水平均显著升高(均P<0.01),Ki-67、MMP-2、MMP-9蛋白和circ_0003998的表达水平、细胞迁移和侵袭细胞数均显著降低(均P<0.01),并呈现浓度依赖性。circ_0003998可以靶向负调控miR-145的表达。敲减circ_0003998后,MDA-MB-231细胞的增殖抑制率、miR-145表达水平显著升高,Ki-67、MMP-2和MMP-9蛋白表达水平、细胞迁移和侵袭细胞数均显著减少(均P<0.01)。共转染si-circ_0003998和anti-miR-145则可逆转敲减circ_0003998表达对MDA-MB-231细胞增殖、迁移和侵袭的抑制作用,过表达circ_0003998或抑制miR-145表达可逆转PSPA对MDA-MB-231细胞增殖、迁移和侵袭的抑制作用。结论:PSPA通过circ_0003998/miR-145轴抑制乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭。
4.SNHG6 promotes invasion and metastasis of esophageal squamous cell carcinoma TE1 cells via upregulating ZEB1
WANG Mengjie ; LIU Yan ; LYU Wei ; TIAN Cong ; WANG Yu ; ZHAO Lianmei ; LIU Lihua
Chinese Journal of Cancer Biotherapy 2020;27(3):282-288
Objective: To explore the roles and mechanisms of long non-coding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6) in promoting invasion and metastasis of esophageal squamous carcinoma (ESCC). Methods: Real time quantitative polymerase chain reaction (qPCR) was used to detect the expression of SNHG6 in ESCC and matched para-carcinoma tissues. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the expression of SNHG6 in ESCC cell lines (TE1, Yes-2, Eca9706 and Kyse150). Then, TE1 cell line which harbored highest expression of SNHG6 was used in following experiments. siRNAs were used to knock down the expression of SNHG6. Clone formation, wound-healing and transwell assay were used to detect the abilities of proliferation, migration andinvasionofTE1cells,respectively.Westernblottingwasusedtodetecttheexpressions of MMP-2, MMP-9andZEB1 protein before and after knockdownofSNHG6inTE1cells.Results:SNHG6washighlyexpressedinESCC tissues, compared to para-carcinoma tissues (P<0.01). The expression of SNHG6 was significantly decreased after transfection of SNHG6siRNA (all P<0.01). The abilities of proliferation, migration and invasion of TE1 cells in si-SNHG6-1 and si-SNHG6-2 group were significantly lower than those in the control group (all P<0.01). The expressions of ZEB1, MMP-2and MMP-9 in si-SNHG6-1 and si-SNHG6-2 group were significantly lower than those in the control group (all P<0.05). Conclusion: SNHG6 is highly expressed in ESCC tissues and promotes the malignant biological behavior of ESCC cells. Its mechanism of promoting the occurrence and development of ESCC may be related to the upregulation of ZEB1 expression.
5.miR-142-5p inhibits the invasion and migration of lung adenocarcinoma H1650 cells by affecting epithelial mesenchymal transformation
WANG Miao ; WANG Yu ; LYU Wei ; DUAN Yuqing ; JIA Yunlong ; LIU Lihua
Chinese Journal of Cancer Biotherapy 2020;27(2):142-148
Objective: To study the expression of miR-142-5p in lung adenocarcinoma tissues, and to explore its effect on proliferation, invasion, migration and epithelieal-mesenchymal transition (EMT) of H1650 cells and the potential mechanisms. Methods:Atotal of 107 pairs of lung adenocarcinoma tissues and corresponding para-cancerous tissues from patients, who underwent tumor resection and were pathologically confirmed at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University between Jan. 2014 and Jan. 2015, were collected for this study; in addition, human lung adenocarcinoma cell lines (H1650, HCC827, A549, H1975, PC9) and human bronchial epithelial BEAS-2B cells were also used in this study. qPCR was used to detect the expression of miR-142-5p in lung adenocarcinoma tissues and cell lines. The correlation between expression of miR-142-5p and clinical features was analyzed.After transfection with miR-142-5p mimics or miR-negative control (miR-NC) plasmid, the proliferation, invasion and migration of H1650 cells were detected with CCK-8, Transwell invasion assay and Wound healing assay, respectively. The bioinforamtics tool was used to predict the target genes of miR-142-5p, and Luciferase reporter gene assay was performed to validate the regulation of miR-142-5p on target gene. Western blotting (WB) was used to detect the expressions of cyclin-dependent kinase 5 (CDK5) and EMTrelated protein. Results: Compared to Para-cancerous tissues and BEAS-2B cells, the expression of miR-142-5p was lower in lung adenocarcinoma tissues and cell lines (all P<0.01). Of the 107 cases of lung adenocarcinoma tissues, 61 cases (57.01%) showed decreased miR-142-5 expression, which was correlated with the TNM stage and lymph node metastasis (both P<0.01). Transfection of miR-142-5p mimics significantly up-regulated the expression of miR-142-5p and decreased the proliferation, invasion and migration of H1650 cells (all P<0.05 or P<0.01). Bioinformatics showed that CDK5 was a target gene of miR-142-5p. Luciferase reporter gene assay and WB validated that miR-142-5p could significantly down-regulate CDK5 expression in H1650 cells, up-regulate the expression of E-cadherin and down-regulate the expressions of N-cadherin, Twist and Snail in H1650 cells (all P<0.01). Conclusion: miR-142-5p is low expressed in lung adenocarcinoma tissues and cell lines; it suppresses the EMT process to inhibit, invasion and migration of H1650 cells via down-regulating the expression of CDK5.
6.Apatinib enhances the anti-tumor effect of cisplatin on gastric cancer by inhibiting HMGA2
ZHAN Fajie ; ZHU Haiyan ; LYU Yuxina ; SU Guohong ; LU Yimin ; LI Chengbiao
Chinese Journal of Cancer Biotherapy 2020;27(10):1131-1137
[Abstract] Objective: To investigate the effect of apatinib (APA) combined with cisplatin (DDP) on the proliferation, invasion and
migration capacity of gastric carcinoma (GC) cells and its molecular mechanism. Methods: Cancer and para-cancerous tissue samples
resected from 50 GC patients, who were surgically treated in Wuwei People's Hospital from January 2016 to June 2019, were
collected for this study; in addition, GC cell lines MGC803 and SGC7901 were also collected. qPCR was used to detect the HMGA2
expression in tissues and mRNA expressions of molecules related to cell proliferation, migration and invasion in GC cell lines.
MGC803 and SGC7901 cells were transfected with pcHMGA2 by liposome transfection technology. After treatment with DDP and
APA at different concentrations, the cells were divided into NC, pcHMGA2, pcHMGA2+DDP and pcHMGA2+DDP+APA groups.
Protein expression of HMGA2 in GC cells was detected by Western blotting, and proliferation, migration and invasion of the cells were
detected by MTT and Transwell assay, respectively. Results: The mRNA expression of HMGA2 in GC tissues was higher than that in
para-cancerous tissues (P<0.05), and the survival rate of GC patients in the high expression group was significantly reduced (P<0.01).
DDP significantly inhibited the proliferation, invasion and migration of MGC803 and SGC7901 cells (all P<0.01); the proliferation,
invasion and migration of MGC803 and SGC7901 cells in DDP+APA group significantly decreased (all P<0.01) as compared with
DDP group; APA significantly enhanced the inhibitory effect of DDP on HMGA2 expression in GC cells (P<0.01); APA enhanced
the anticancer activity of DDP against GC by down-regulating HMGA2 expression. Conclusion: APA promotes the anticancer
activity of DDP against GC, and its molecular mechanism is the promotion of the inhibitory effect of DDP on HMGA2 expression.
7.lncRNA00707 regulates malignant biological behavior of gastric cancer MGC-803 and SGC-7901 cells via miR-613
LYU Haidong ; ZHOU Dixia ; QI Yujuan
Chinese Journal of Cancer Biotherapy 2019;26(9):999-1005
To investigate the role of long chain non-coding RNA00707 (lncRNA00707) and micro RNA-613 (miR-613) in regulating the proliferation and metastasis of gastric cancer cells and its underlying mechanisms. Methods: Eighty-nine pairs of primary gastric cancer tissues and corresponding prar-cancerous tissues were collected from the Department of Surgical Oncology, Qinghai Provincial People's Hospital during January 2014 and June 2018 for this study. The expressions of lncRNA00707 and miR-613 in gastric cancer tissues and cells were detected by qPCR. The lncRNA00707 low expression and over-expression models of MGC-803 and SGC-7901 cells were established; The proliferation of gastric cancer cells was monitored by CCK-8 assay, and Transwell assay was performed to determine the migration and invasion of gastric cancer cells. Dual luciferase gene reporter assay was adopted to validate the relationship between lncRNA 00707 and miR-613. Results: Compared with para-cancerous tissues and normal cell line GES-1, the expression of lncRNA 00707 was significantly up-regulated in cancer tissues and cell lines, and the expression of lncRNA00707 was positively correlated with WHO stage (all P<0.05). Down-regulation of lncRNA 00707 significantly inhibited the proliferation and migration of SGC-7901 cells, while overexpression of lncRNA00707 exerted the opposite effect (all P<0.05). Compared with negative control group, lncRNA00707 over-expression significantly reduced the luciferase activity of miR-613; in the contrary, the luciferase activity of miR-163 was significantly increased in MGC-803 and SGC-7901 cells with lncRNA 00707 knockdown (all P<0.01). Conclusion: lncRNA 00707 facilitates the proliferation, migration and invasion of gastric cancer cells by inhibiting the function of miR-613, which exerts a protumorigenic effect in gastric cancer.
8.Study on genetic structure differences and adjustment strategies in different areas of China.
M ZHU ; J LYU ; C Q YU ; G F JIN ; Y GUO ; Z BIAN ; W ROBIN ; M IONA ; Z M CHEN ; H B SHEN ; Z B HU ; L M LI
Chinese Journal of Epidemiology 2019;40(1):20-25
<b>Objective:b> To describe the genetic structure of populations in different areas of China, and explore the effects of different strategies to control the confounding factors of the genetic structure in cohort studies. <b>Methods:b> By using the genome-wide association study (GWAS) on data of 4 500 samples from 10 areas of the China Kadoorie Biobank (CKB), we performed principal components analysis to extract the first and second principal components of the samples for the component two-dimensional diagram generation, and then compared them with the source of sample area to analyze the characteristics of genetic structure of the samples from different areas of China. Based on the CKB cohort data, a simulation data set with cluster sample characteristics such as genetic structure differences and extensive kinship was generated; and the effects of different analysis strategies including traditional analysis scheme and mixed linear model on the inflation factor (λ) were evaluated. <b>Results:b> There were significant genetic structure differences in different areas of China. Distribution of the principal components of the population genetic structure was basically consistent with the geographical distribution of the project area. The first principal component corresponds to the latitude of different areas, and the second principal component corresponds to the longitude of different areas. The generated simulation data showed high false positive rate (λ=1.16), even if the principal components of the genetic structure was adjusted or the area specific subgroup analysis was performed, λ could not be effectively controlled (λ>1.05); while, by using a mixed linear model adjusting for the kinship matrix, λ was effectively controlled regardless of whether the genetic structure principal component was further adjusted (λ=0.99). <b>Conclusions:b> There were large differences in genetic structure among populations in different areas of China. In molecular epidemiology studies, bias caused by population genetic structure needs to be carefully treated. For large cohort data with complex genetic structure and extensive kinship, it is necessary to use a mixed linear model for association analysis.
China
;
Genetic Structures
;
Genome-Wide Association Study
;
Humans
;
Linear Models
;
Principal Component Analysis
9.Prevalence of 'healthy lifestyle' in Chinese adults.
N B ZHU ; M ZHOU ; C Q YU ; Y GUO ; Z BIAN ; Y L TAN ; P PEI ; J S CHEN ; Z M CHEN ; J LYU ; L M LI
Chinese Journal of Epidemiology 2019;40(2):136-141
<b>Objective:b> To examine the prevalence of 'healthy lifestyle' from data extracted from the China Kadoorie Biobank (CKB) of 0.5 million adults from ten areas across China. <b>Methods:b> After excluding participants with self-reported histories of coronary heart disease, stroke or cancer, a total of 487 198 participants at baseline (2004-2008) and 22 604 participants at second survey (2013- 2014), were included for analysis. 'Healthy lifestyle' was defined as haing the following characteristics: a) never smoking or having stopped smoking for reasons other than illness; b) alcohol drinking <25 g/day (men)/<15 g/day (women); c) diet rich in vegetables, fruits, legumes and fish, but low in red meat; d) upper quarter of the physical activity level; e) body mass index of 18.5-23.9 kg/m(2) and waist circumstance <85 cm (men)/80 cm (women). We calculated the healthy lifestyle scores (HLS) by counting the number of all the healthy lifestyle factors, with a range from 0 to 6. <b>Results:b> At baseline, prevalence rates of the above five healthy lifestyles (except physical activity) were 70.6%, 92.6%, 8.7%, 52.6% and 59.0%, respectively, with the mean HLS being 3.1±1.2. Most participants (81.4%) had2-4 healthy components, while only 0.7% (0.2% in men and 1.0% in women) of all the participants had all six healthy lifestyles. Participants who were women, at younger age, with more schooling and rural residents, were more likely to adhere to the healthy lifestyle. After ten years, the mean HLS showed a slight decrease. <b>Conclusion:b> The prevalence of optimal lifestyles in Chinese adults appeared extremely low. Levels of 'healthy lifestyle' varied greatly among those populations with different socio-demographic characteristics across the ten areas in China.
Adult
;
Asian People/statistics & numerical data*
;
China
;
Female
;
Healthy Lifestyle
;
Humans
;
Life Style
;
Male
;
Prevalence
;
Risk Factors
10.Pathogenic surveillance and related factors on bacillary dysentery in Beijing, 2008-2017.
L JIA ; B LYU ; Y TIAN ; X ZHANG ; Z C LIU ; H PENG ; H J LI ; B J ZHEN ; X L WANG ; Y HUANG ; M QU ; Q Y WANG
Chinese Journal of Epidemiology 2019;40(2):165-169
<b>Objective:b> To analyze the pathogenic surveillance programs and related factors on bacillary dysentery in Beijing, 2008-2017, to provide evidence for the practices of diagnosis, treatment and prevention of the disease. <b>Methods:b> Analysis was conducted on surveillance data of bacillary dysentery, collected from the surveillance areas of national bacillary dysentery in Beijing. Shigella positive rate of stool samples were used as the gold standard while detection rate of Shigella, diagnostic accordance rate and resistance were computed on data from the surveillance programs. Chi-square test was used to compare the rates and unconditional logistic regression was used to analyze the related factors of Shigella infection. <b>Results:b> Both the reported incidence rate on bacillary dysentery and detection rate of Shigella in diarrhea patients showed significantly decreasing trend, from 2008 to 2017. The accordance rate of bacillary dysentery was only 7.80% (111/1 423). Shigella sonnei was the most frequently isolated strain (73.95%, 159/215) followed by Shigella flexnery. Results from the multivariate logistic regression of Shigella positive rate revealed that among those patients who were routine test of stool positive vs. routine test of stool positive (OR=1.863, 95%CI: 1.402-2.475), onset from July to October vs. other months'time (OR=7.271, 95%CI: 4.514-11.709) temperature ≥38 ℃vs. temperature <38 ℃(OR=4.516, 95%CI: 3.369-6.053) and age from 6 to 59 years old vs. other ages (OR=1.617, 95%CI: 1.085-2.410), presenting higher positive detection rates of Shigella from the stool tests. The resistant rates on ampicillin and nalidixic acid were 97.57% (201/206) and 94.90% (186/196), both higher than on other antibiotics. The resistant rates on ciprofloxacin (16.33%, 32/196), ofloxacin (9.57%, 11/115) and on amoxilin (15.05%, 31/206) were relatively low. The resistant rate appeared higher on Shigella flexnery than on Shigella sonnei. The proportion of strains with resistance on 3 more drugs, was 30.00%(21/70). <b>Conclusions:b> The diagnostic accordance rate of bacillary dysentery in Beijing was low, with severe resistance of Shigella. Our findings suggested that clinicians should take multiple factors into account in their practices about epidemiological history, clinical symptom and testing results for diarrhea patients.
Adolescent
;
Adult
;
Anti-Bacterial Agents/therapeutic use*
;
Beijing/epidemiology*
;
Child
;
China/epidemiology*
;
Dysentery, Bacillary/prevention & control*
;
Feces/microbiology*
;
Humans
;
Middle Aged
;
Population Surveillance/methods*
;
Sentinel Surveillance
;
Shigella/isolation & purification*
;
Shigella flexneri/isolation & purification*
;
Shigella sonnei/isolation & purification*
;
Young Adult

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