Citation: | ZHENG Jianjiang, ZHENG Bingli, LIU Yuequan. Molecular mechanism of regulating miR-223-3p/RHOB expression by circRNA SAMD8 to inhibit progression of pancreatic ductal adenocarcinoma[J]. Journal of Clinical Medicine in Practice, 2024, 28(5): 31-39. DOI: 10.7619/jcmp.20232852 |
To investigate the potential mechanism of circRNA SAMD8(circ-SAMD8) in development of pancreatic ductal adenocarcinoma (PDAC).
The expression profile of circRNAs in PDAC tissues was analyzed based on Microarray data (GSE79634). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of circ-SAMD8 (hsa_circ_0006148) in PDAC tissues and cells (CFPAC-1 and PANC-1).The target microRNA (miRNA) of circ-SAMD8 and its downstream mRNA were predicted by bioinformatics analysis, and identified by double luciferase reporter gene assay. The proliferation ability of PDAC cells was detected by MTT assay and colony formation assay. The expression levels of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax were detected by Western blot. The percentage of apoptotic cells was detected by flow cytometry.
The expression levels of circ-SAMD8 in PDAC tissues and cells were significantly lower than those in paracancer tissues and normal cells (P < 0.05). Overexpression of circ-SAMD8 could effectively promote apoptosis of PDAC cells and inhibited proliferation of PDAC cells.Dual luciferase reporter gene experiments showed that miR-223-3p was a potential interacting molecule of circ-SAMD8, and the downstream mRNA target of miR-223-3p was RHOB. The miR-223-3p was abnormally overexpressed in PDAC tissues and cells, accompanied by low RHOB expression. In PDAC cells transfected with miR-223-3p mimics or sh-circ-SAMD8, RHOB expression was significantly decreased, proliferation ability was enhanced, and apoptosis rate was decreased.
Circ-SAMD8 regulates the expression of RHOB downstream by sponging miR-223-3p, and effectively inhibits the occurrence and development of PDAC.
[1] |
潘泓, 廖颖娜, 盖严支, 等. 分选链接蛋白1在胰腺导管腺癌中的表达及其促进胰腺导管腺癌进展的机制研究[J]. 上海交通大学学报: 医学版, 2023, 43(3): 278-292. doi: 10.3969/j.issn.1674-8115.2023.03.003
|
[2] |
ZHENG L, XUE J, JAFFEE E M, et al. Role of immune cells and immune-based therapies in pancreatitis and pancreatic ductal adenocarcinoma[J]. Gastroenterology, 2013, 144(6): 1230-1240. doi: 10.1053/j.gastro.2012.12.042
|
[3] |
GIFFORD J B, HUANG W, ZELENIAK A E, et al. Expression of GRP78, master regulator of the unfolded protein response, increases chemoresistance in pancreatic ductal adenocarcinoma[J]. Mol Cancer Ther, 2016, 15(5): 1043-1052. doi: 10.1158/1535-7163.MCT-15-0774
|
[4] |
钱心怡, 刘鹏渊, 陆燕. 非编码RNA在肿瘤发生发展和诊治中的作用[J]. 中国科学: 生命科学, 2022, 52(12): 1796-1806.
|
[5] |
HAN D, LI J X, WANG H M, et al. Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression[J]. Hepatology, 2017, 66(4): 1151-1164. doi: 10.1002/hep.29270
|
[6] |
BHASKARAN M, MOHAN M. MicroRNAs: history, biogenesis, and their evolving role in animal development and disease[J]. Vet Pathol, 2014, 51(4): 759-774. doi: 10.1177/0300985813502820
|
[7] |
SHEN F, CAI W S, FENG Z, et al. MiR-492 contributes to cell proliferation and cell cycle of human breast cancer cells by suppressing SOX7 expression[J]. Tumour Biol, 2015, 36(3): 1913-1921. doi: 10.1007/s13277-014-2794-z
|
[8] |
FRAMPTON A E, GIOVANNETTI E, JAMIESON N B, et al. A microRNA meta-signature for pancreatic ductal adenocarcinoma[J]. Expert Rev Mol Diagn, 2014, 14(3): 267-271. doi: 10.1586/14737159.2014.893192
|
[9] |
DU W W, YANG W N, LIU E, et al. Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2[J]. Nucleic Acids es, 2016, 44(6): 2846-2858. doi: 10.1093/nar/gkw027
|
[10] |
BACHMAYR-HEYDA A, REINER A T, AUER K, et al. Correlation of circular RNA abundance with proliferation: exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues[J]. Sci Rep, 2015, 5: 8057. doi: 10.1038/srep08057
|
[11] |
LI P F, CHEN S C, CHEN H L, et al. Using circular RNA as a novel type of biomarker in the screening of gastric cancer[J]. Clin Chim Acta, 2015, 444: 132-136. doi: 10.1016/j.cca.2015.02.018
|
[12] |
CHEN G W, SHI Y T, ZHANG Y, et al. CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway[J]. Onco Targets Ther, 2017, 10: 5783-5794. doi: 10.2147/OTT.S150678
|
[13] |
HUANG W J, WANG Y C, LIU S S, et al. Silencing circular RNA hsa_circ_0000977 suppresses pancreatic ductal adenocarcinoma progression by stimulating miR-874-3p and inhibiting PLK1 expression[J]. Cancer Lett, 2018, 422: 70-80. doi: 10.1016/j.canlet.2018.02.014
|
[14] |
WEI Y B, YANG J R, YI L, et al. MiR-223-3p targeting SEPT6 promotes the biological behavior of prostate cancer[J]. Sci Rep, 2014, 4: 7546. doi: 10.1038/srep07546
|
[15] |
LIU J K, SHI H, LI X D, et al. MiR-223-3p regulates cell growth and apoptosis via FBXW7 suggesting an oncogenic role in human testicular germ cell tumors[J]. Int J Oncol, 2017, 50(2): 356-364. doi: 10.3892/ijo.2016.3807
|
[16] |
FENG Q, HE P, WANG Y. MicroRNA-223-3p regulates cell chemo-sensitivity by targeting FOXO3 in prostatic cancer[J]. Gene, 2018, 658: 152-158. doi: 10.1016/j.gene.2018.03.013
|
1. |
王轶. 注射用盐酸倍他司汀治疗眩晕症的临床效果及对炎性因子的影响. 临床合理用药. 2024(02): 48-51 .
![]() | |
2. |
曾智本,吴新风. 三联疗法联合倍他司汀治疗耳石症复位后残余头晕的效果观察. 实用临床医药杂志. 2024(13): 92-97 .
![]() | |
3. |
李欣龙,袁琳. 倍他司汀联合阿托伐他汀用于颈动脉斑块伴眩晕患者的疗效观察. 大医生. 2023(05): 41-43 .
![]() | |
4. |
栗冰洁. 半夏白术天麻汤联合氟桂利嗪胶囊治疗周围性眩晕患者的效果. 承德医学院学报. 2023(02): 124-127 .
![]() | |
5. |
刘钢招,钟丽,沈娟. 倍他司汀联合天麻钩藤饮治疗眩晕症的疗效及对脑血流动力学的影响. 现代诊断与治疗. 2023(05): 644-646 .
![]() | |
6. |
金赢政,井睿智,李金江. 天麻钩藤饮联合针灸治疗后循环缺血性眩晕临床研究. 新中医. 2023(22): 53-58 .
![]() | |
7. |
刘秀. 倍他司汀联合盐酸氟桂利嗪对颈性眩晕患者眩晕症状及血液流变学的影响. 现代医学与健康研究电子杂志. 2023(23): 47-49 .
![]() | |
8. |
章恒端,叶旭星,胡建海. 半夏白术天麻汤联合耳穴埋豆治疗颈性眩晕的临床效果. 中国医师杂志. 2022(12): 1832-1836 .
![]() | |
9. |
冷静,李红,王孝佳,董阳,韩丽丽. 后循环缺血继发眩晕给予倍他司汀及氟桂利嗪的临床干预效果评析. 中外医疗. 2022(29): 89-92 .
![]() | |
10. |
许电,陈慧珍,邓恺伦. 针刺联合甲磺酸倍他司汀片对颈性眩晕患者疗效及椎基底动脉血流动力学的影响. 医学理论与实践. 2021(18): 3163-3164 .
![]() | |
11. |
李晓,贺永雄,李世珅. 不同方法治疗颈性眩晕症的临床疗效比较. 内蒙古医学杂志. 2020(12): 1423-1424 .
![]() |