
浏览全部资源
扫码关注微信
1.710061 西安,西安交通大学第一附属医院: 营养科
2.710061 西安,西安交通大学第一附属医院: 肝胆外科
3.710061 西安,西安交通大学第一附属医院: 老年外科
[张雷,E-mail: zhanglei0519@xjtu.edu.cnZHANG Lei, E-mail: zhanglei0519@xjtu.edu.cn
收稿:2020-12-31,
修回:2021-02-08,
纸质出版:2021-07-15
移动端阅览
鲜瑶, 刘润坤, 莫缓椰, 等. miR-3934-5p靶向抑制β内酰胺酶表达促进肝癌细胞增殖[J]. 第三军医大学学报, 2021,43(13):1219-1226.
Yao XIAN, Runkun LIU, Huanye MO, et al. MiR-3934-5p promotes proliferation of hepatocellular carcinoma cells by targeting LACTB[J]. Journal of Third Military Medical University, 2021, 43(13): 1219-1226.
鲜瑶, 刘润坤, 莫缓椰, 等. miR-3934-5p靶向抑制β内酰胺酶表达促进肝癌细胞增殖[J]. 第三军医大学学报, 2021,43(13):1219-1226. DOI: 10.16016/j.1000-5404.202012245.
Yao XIAN, Runkun LIU, Huanye MO, et al. MiR-3934-5p promotes proliferation of hepatocellular carcinoma cells by targeting LACTB[J]. Journal of Third Military Medical University, 2021, 43(13): 1219-1226. DOI: 10.16016/j.1000-5404.202012245.
目的
2
观察miR-3934-5p在肝细胞癌(hepatocellular carcinoma
HCC)中的表达,探讨其临床意义及分子机制。
方法
2
收集53例2013年9月至2014年8月在本院确诊的肝细胞癌患者的癌旁组织及肿瘤组织。实时定量PCR(RT-qPCR)检测组织和细胞miR-3934-5p的表达;应用人类癌症基因库(the Cancer Genome Atlas
TCGA)分析正常肝组织与肝癌组织中miR-3934-5p的表达;用χ
2
检验和Kaplan-Meier生存曲线分析miR-3934-5p与临床病理特征及生存预后之间的相关性;采用RT-qPCR和Western blot检测转染效率;CCK-8实验、平板克隆实验及EdU实验评价HCCLM3细胞的活性及增殖能力;分析HCC组织中β-内酰胺酶(beta-lactamases,LACTB) mRNA与miR-3934-5p表达的相关性;TargetScan数据库预测miR-3934-5p下游靶基因,通过荧光素酶报告基因实验加以验证。
结果
2
miR-3934-5p在肝癌组织及细胞中高表达(
P
<
0.05),且其高表达与肿瘤大小、肿瘤数量、血管侵犯及TNM分期显著相关(
P
<
0.05);与miR-3934-5p低表达组相比,miR-3934-5p高表达组的肝癌患者5年生存率更低;CCK-8实验、平板克隆实验及EdU实验结果证实: 敲减miR-3934-5p可显著抑制HCCLM3细胞的增殖能力(
P
<
0.05);LACTB被证实是miR-3934-5p的直接作用靶点,且其介导了miR-3934-5p的生物学功能。
结论
2
miR-3934-5p通过靶向抑制抑癌基因LACTB的表达促进肝癌细胞的增殖能力。
Objective
2
To explore the expression
clinical significance and molecular mechanism of miR-3934-5p in hepatocellular carcinoma (HCC).
Methods
2
HCC tissues and adjacent normal tissues were collected from 53 HCC patients diagnosed in our hospital from September 2013 to August 2014. Real-time quantitative PCR (RT-qPCR) was performed to detect the level of miR-3934-5p in the above tissues and human liver cell line L02 and HCC cell lines. The Cancer Genome Atlas (TCGA) database was used to analyze the expression of miR-3934-5p in normal liver tissues and HCC tissues;
Chi
-square test with Kaplan-Meier survival curve were applied to analyze the correlation of miR-3934-5p and clinicopathological characteristics and survival prognosis; RT-qPCR and Western blotting were adopted to detect transfection efficiency; CCK-8 assay
colony formation assay and EdU assay were employed respectively to evaluate the activity and proliferation of HCCLM3 cells; Spearman correlation analysis was applied to study the correlation between LACTB mRNA and miR-3934-5p expression i
n HCC tissues; TargetScan database was used to predict the downstream target genes of miR-3934-5p
and the prediction results was verified by luciferase reporter assay.
Results
2
MiR-3934-5p was highly expressed in the liver cancer tissues and cells (
P
<
0.05)
and its high expression was significantly correlated with tumor size (
P
=0.040)
tumor multiplicity (
P
=0.013)
vascular invasion (
P
=0.006)
and TNM stage (
P
=0.017); Compared to the low miR-3934-5p expression group
the HCC patients with high expression had poorer survival prognosis. CCK-8 assay
colony formation assay and EdU assay confirmed that knocking down miR-3934-5p notably inhibited the proliferation of HCCLM3 cells (
P
<
0.05). LACTB had been proved to be the direct target of miR-3934-5p
and mediated the biological effect of miR-3934-5p on HCC cells.
Conclusion
2
MiR-3934-5p promotes the proliferation of HCC cells by targeting tumor suppressor gene LACTB.
BRAY F, FERLAY J, SOERJOMATARAM I, et al . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J ] . CA Cancer J Clin, 2018, 68(6): 394-424. DOI:10.3322/caac.21492.
LI Y, WANG X Y, LI Z G, et al . MicroRNA-4651 represses hepatocellular carcinoma cell growth and facilitates apoptosis via targeting FOXP4[J ] . Biosci Rep, 2020, 40(6): BSR20194011. DOI:10.1042/BSR20194011..
MAJID A, WANG J X, NAWAZ M, et al . miR-124-3p suppresses the invasiveness and metastasis of hepatocarcinoma cells via targeting CRKL[J ] . Front Mol Biosci, 2020, 7: 223. DOI:10.3389/fmolb.2020.00223..
REN A J, WEN Z Z, ZHENG L J. Downregulation of miR-3934-5p enhances A549 cell sensitivity to cisplatin by targeting TP53INP 1 [J ] . Exp Ther Med, 2019, 18(3): 1653-1660. DOI:10.3892/etm.2019.7718.
YE W, LIANG F, YING C, et al . Downregulation of microRNA-3934-5p induces apoptosis and inhibits the proliferation of neuroblastoma cells by targeting TP53INP 1 [J ] . Exp Ther Med, 2019, 18(5): 3729-3736. DOI:10.3892/etm.2019.8007..
CUCCHI D, MAURO C. LACTB-mediated tumour suppression by increased mitochondrial lipid metabolism[J]. Cell Death Differ, 2017, 24(7): 1137-1139. DOI: 10.1038/cdd.2017.60.
KECKESOVA Z, DONAHER J L, DE COCK J, et al . LACTB is a tumour suppressor that modulates lipid metabolism and cell state[J ] . Nature, 2017, 543(7647): 681-686. DOI:10.1038/nature21408.
ZENG K, CHEN X, HU X, et al . LACTB, a novel epigenetic silenced tumor suppressor, inhibits colorectal cancer progression by attenuating MDM2-mediated p53 ubiquitination and degradation[J ] . Oncogene, 2018, 37(41): 5534-5551. DOI:10.1038/s41388-018-0352-7.
XUE C, HE Y, ZHU W, et al . Low expression of LACTB promotes tumor progression and predicts poor prognosis in hepatocellular carcinoma[J ] . Am J Transl Res, 2018, 10(12): 4152-4162.
LI Y, ZHOU Y, MA L, et al . MiR-3677-3p promotes hepatocellular carcinoma progression via inhibiting GSK3β[J ] . Acta Biochim Biophys Sin (Shanghai), 2020, 52(12): 1404-1412. DOI:10.1093/abbs/gmaa125..
SI T, NING X J, ZHAO H W, et al . MicroRNA-9-5p regulates the mitochondrial function of hepatocellular carcinoma cells through suppressing PDK4[J ] . Cancer Gene Ther, 2020: 1-13. DOI:10.1038/s41417-020-00253-w.
DUAN X H, LI W, HU P, et al . MicroRNA-183-5p contributes to malignant progression through targeting PDCD4 in human hepatocellular carcinoma[J ] . Biosci Rep, 2020, 40(10): BSR20201761. DOI:10.1042/BSR20201761.
ZHAO Y C, ZHU C Q, CHANG Q, et al . MiR-424-5p regulates cell cycle and inhibits proliferation of hepatocellular carcinoma cells by targeting E2F 7 [J ] . PLoS One, 2020, 15(11): e0242179. DOI:10.1371/journal.pone.0242179..
WANG Q, YANG X, ZHOU X, et al . MiR-3174 promotes proliferation and inhibits apoptosis by targeting FOXO1 in hepatocellular carcinoma[J ] . Biochem Biophys Res Commun, 2020, 526(4): 889-897. DOI:10.1016/j.bbrc.2020.03.152.
YAO B W, NIU Y S, LI Y Z, et al . High-matrix-stiffness induces promotion of hepatocellular carcinoma proliferation and suppression of apoptosis via miR-3682-3p-PHLDA1-FAS pathway[J ] . J Cancer, 2020, 11(21): 6188-6203. DOI:10.7150/jca.45998..
XIAN Y, WANG L, YAO B, et al . MicroRNA-769-5p contributes to the proliferation, migration and invasion of hepatocellular carcinoma cells by attenuating RYBP[J ] . Biomed Pharmacother, 2019, 118: 109343. DOI:10.1016/j.biopha.2019.109343.
张雷, 王宇锋, 王亮, 等. miR-130b-3p通过靶向作用于INTS6促进肝细胞癌生长和转移[J]. 山西医科大学学报, 2019, 50(5): 543-550. DOI: 10.13753/j.issn.1007-6611.2019.05.003.
ZHANG L, WANG Y F, WANG L, et al . The miR-130b-3p promotes metastasis and proliferation of hepatocellular carcinoma by targeting INTS6[J ] . J Shanxi Med Univ, 2019, 50(5): 543-550, DOI: 10.13753/j.issn.1007-6611.2019.05.003.
YU Y, MIN Z, ZHOU Z, et al . Hypoxia-induced exosomes promote hepatocellular carcinoma proliferation and metastasis via miR-1273f transfer[J ] . Exp Cell Res, 2019, 385(1): 111649. DOI: 10.1016/j.yexcr.2019.111649..
POLIANSKYTE Z, PEITSARO N, DAPKUNAS A, et al . LACTB is a filament-forming protein localized in mitochondria[J ] . Proc Natl Acad Sci USA, 2009, 106(45): 18960-18965. DOI:10.1073/pnas.0906734106.
LI H T, DONG D Y, LIU Q, et al . Overexpression of LACTB, a mitochondrial protein that inhibits proliferation and invasion in glioma cells[J ] . Oncol Res, 2019, 27(4): 423-429. DOI:10.3727/096504017X15030178624579.
LANG V, PALLARA C, ZABALA A, et al . Tetramerization-defects of p53 result in aberrant ubiquitylation and transcriptional activity[J ] . Mol Oncol, 2014, 8(5): 1026-1042. DOI:10.1016/j.molonc.2014.04.002.
RUSSO A, ESPOSITO D, CATILLO M, et al . Human rpL3 induces G 1 /S arrest or apoptosis by modulating p21 (Waf1/cip1) levels in a p53-independent manner[J ] . Cell Cycle, 2013, 12(1): 76-87. DOI:10.4161/cc.22963..
WALERYCH D, LISEK K, SOMMAGGIO R, et al . Proteasome machinery is instrumental in a common gain-of-function program of the p53 missense mutants in cancer[J ] . Nat Cell Biol, 2016, 18(8): 897-909. DOI:10.1038/ncb3380.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621