LINC00525靶向miR-338-3p促进胃癌细胞凋亡和降低其耐药性

孙玉成; 刘晓巍; 于红雷

doi:10.16016/j.1000-5404.202006247

您当前的位置：

首页 >

文章列表页 >

LINC00525靶向miR-338-3p促进胃癌细胞凋亡和降低其耐药性

基础医学 | 更新时间：2026-01-09

- LINC00525靶向miR-338-3p促进胃癌细胞凋亡和降低其耐药性
- LINC00525 targeting miR-338-3p promotes apoptosis and reduces paclitaxel resistance in gastric cancer cells
- 第三军医大学学报 2020年42卷第22期页码：2202-2209
- 作者机构：
  
  133000 吉林延吉, 延边大学附属医院普外一科
- 作者简介：
  
  [ 孙玉成，E-mail:ybyysyc@163.com SUN Yucheng, E-mail:ybyysyc@163.com
- 基金信息：
- DOI：10.16016/j.1000-5404.202006247
  中图分类号： R73-362;R735.2;R915
- 收稿：2020-06-29，
  
  修回：2020-08-13，
  
  纸质出版：2020-11-30
- 稿件说明：
移动端阅览
孙玉成, 刘晓巍, 于红雷. LINC00525靶向miR-338-3p促进胃癌细胞凋亡和降低其耐药性[J]. 第三军医大学学报, 2020,42(22):2202-2209.

Yucheng SUN, Xiaowei LIU, Honglei YU. LINC00525 targeting miR-338-3p promotes apoptosis and reduces paclitaxel resistance in gastric cancer cells[J]. Journal of Third Military Medical University, 2020, 42(22): 2202-2209.
孙玉成, 刘晓巍, 于红雷. LINC00525靶向miR-338-3p促进胃癌细胞凋亡和降低其耐药性[J]. 第三军医大学学报, 2020,42(22):2202-2209. DOI： 10.16016/j.1000-5404.202006247.

Yucheng SUN, Xiaowei LIU, Honglei YU. LINC00525 targeting miR-338-3p promotes apoptosis and reduces paclitaxel resistance in gastric cancer cells[J]. Journal of Third Military Medical University, 2020, 42(22): 2202-2209. DOI： 10.16016/j.1000-5404.202006247.

摘要

目的

研究LINC00525靶向miR-338-3p对胃癌细胞凋亡及耐药性的影响。

方法

将紫杉醇耐药胃癌细胞(HGC-27/PTX)分为si-NC组、si-LINC00525组、miR-NC组、miR-338-3p组、si-LINC00525+anti-miR-NC组、si-LINC00525+anti-miR-338-3p组。细胞计数试剂盒8(cell counting kit 8，CCK-8)检测细胞存活率；实时荧光定量PCR(RT-qPCR)检测LINC00525和miR-338-3p表达水平；蛋白质印迹(Western blot)法检测蛋白表达；Annexin V-FITC/PI双染法检测细胞凋亡；Transwell检测细胞迁移和侵袭；双荧光素酶报告实验验证LINC00525和miR-338-3p的靶向关系。

结果

HGC-27和HGC-27/PTX细胞中LINC00525表达水平升高，miR-338-3p表达水平降低。敲除LINC00525和过表达miR-338-3p，caspase-3、P21、E-cadherin表达水平升高，MMP-2表达水平降低，细胞存活率降低，细胞凋亡率升高，细胞迁移、侵袭数降低。LINC00525靶向调控miR-338-3p，抑制miR-338-3p能减弱敲除LINC00525对细胞HGC-27/PTX的存活率、迁移、侵袭及凋亡的影响。

结论

敲除LINC00525通过上调miR-338-3p表达抑制HGC-27/PTX细胞增殖、迁移和侵袭，促进胃癌细胞凋亡，降低胃癌细胞对紫杉醇的耐药性。

Abstract

Objective

To study the effect of modulating the expression of LINC00525 targeting miR-338-3p on apoptosis and drug resistance of gastric cancer cells.

Methods

Paclitaxel-resistant gastric cancer cells (HGC-27/PTX) were transfected with si-NC

si-LINC00525

miR-NC

miR-338-3p

si-LINC00525+anti-miR-NC

or si-LINC00525+anti-miR-338-3p. Cell counting kit 8 (CCK-8) was used to determine the cell survival rate after the treatments. Real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect LINC00525 and miR-338-3p expression levels

and Western blotting was used to detect the protein expression in the cells. The changes in cell apoptosis and migration and invasion abilities were analyzed using annexin V-FITC/PI double staining and Transwell assays. Dual luciferase reporter assay was performed to verify the targeting relationship between LINC00525 and miR-338-3p.

Results

The expression of LINC00525 was increased and that of miR-338-3p was decreased in both in HGC-27 and HGC-27/PTX cells. Knocking down LINC00525 and overexpression of miR-338-3p significantly increased the expression of caspase-3

P21

and E-cadherin

lowered the expression of MMP-2

decreased the cell survival rate

increased the cell apoptotic rate

and suppressed cell migration and invasion. Dual luciferase reporter assay showed that LINC00525 was capable of regulating the targeted miR-338-3p

and inhibition of miR-338-3p obviously attenuated the effects of LINC00525 knockdown on the survival

migration

invasion

and apoptosis of HGC-27/PTX cells.

Conclusion

LINC00525 knockdown can inhibit the proliferation

migration and invasion

promote apoptosis and reduce paclitaxel resistance of HGC-27/PTX cells by up-regulating miR-338-3.

关键词

Keywords

references

关露露, 赵青芳, 陈小兵.胃癌多药耐药研究进展[J].肿瘤研究与临床, 2017, 29(6): 422-425. DOI: 10.3760/cma.j.issn.1006-9801.2017.06.018.

GUAN L L, ZHAO Q F, CHEN X B. Progress in multidrug resistance of gastric cancer[J]. Cancer Res Clin, 2017, 29(6): 422-425. DOI: 10.3760/cma.j.issn.1006-9801.2017.06.018.

沈丽平, 范理宏.紫杉醇耐药的研究进展[J].现代肿瘤医学, 2014, 22(8): 1975-1978. DOI: 10.3969/j.issn.1672-4992.2014.08.72.

SHEN L P, FAN L H. Research progress of neoplasms resistance[J]. J Mod Oncol, 2014, 22(8): 1975-1978. DOI: 10.3969/j.issn.1672-4992.2014.08.72.

黄世庆, 韦忠恒.长链非编码RNA在胃癌预后和耐药中的研究进展[J].中国癌症防治杂志, 2017, 9(5): 404-408. DOI: 10.3969/j.issn.1674-5671.2017.05.15.

HUANG S Q, WEI Z H.Research progress of long-chain non-coding RNA in the prognosis and drug resistance of gastric cancer[J]. Chin J Oncol Preu Treat, 2017, 9(5): 404-408. DOI: 10.3969/j.issn.1674-5671.2017.05.15.

张弛, 张雷.微RNA在胃癌中的相关机制及诊断治疗的研究进展[J].医学综述, 2019, 25(1): 55-59. DOI: 10.3969/j.issn.1006-2084.2019.01.011.

ZHANG C, ZHANG L. Research progress in microRNA-associated mechanism, diagnosis and treatment of gastriccancer[J]. Me Recapitulate, 2019, 25(1): 55-59. DOI: 10.3969/j.issn.1006-2084.2019.01.011.

房群. LncRNA UCA1通过下调miR-27b表达增强胃癌多药耐药性的研究[D].济南: 山东大学, 2017.

FANG Q. LncRNA UCA1 enhances multidrug resistance of gastric cancer by down-regulating the expression of miR-27b[D]. Jinan: Shandong University, 2017.

郭苹, 程鹏, 王鹏飞, 等. LncRNA-MEG3对胃癌生物学特性及铂类化疗敏感性的研究[J].中国现代医学杂志, 2019, 29(6): 16-21.

GUO P, CHENG P, WNAG P F, et al . Effect of LncRNA-MEG3 on proliferation and apoptosis of gastric cancer and chemosensitivity of cisplatin[J ] . Chin J Mod Med, 2019, 29(6): 16-21.

WANG X W, GUO Q Q, WEI Y, et al . Construction of a competing endogenous RNA network using differentially expressed lncRNAs, miRNAs and mRNAs in non-small cell lung cancer[J ] . Oncol Rep, 2019, 42(6): 2402-2415. DOI: 10.3892/or.2019.7378.

WANG S S, LI J, YANG X P. Long non-coding RNA LINC00525 promotes the stemness and chemoresistance of colorectal cancer by targeting miR-507/ELK3 axis[J]. Int J Stem Cells, 2019, 12(2): 347-359. DOI: 10.15283/ijsc19041.

LIU S N, SUO J, WANG C X, et al .Downregulation of tissue miR-338-3p predicts unfavorable prognosis of gastric cancer[J ] . Cancer Biomark, 2017, 21(1): 117-122. DOI: 10.3233/cbm-170339.

SUN F, YU M C, YU J, et al . miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B[J ] . Cell Death Dis, 2018, 9(5): 522. DOI: 10.1038/s41419-018-0611-0.

LIU X W, CAI H, SHENG W Q, et al . microRNAs expression profile related with response to preoperative radiochemotherapy in patients with locally advanced gastric cancer[J ] . BMC Cancer, 2018, 18(1): 1-8. DOI: 10.1186/s12885-018-4967-4.

HAN J, LI J, TANG K J, et al . miR-338-3p confers 5-fluorouracil resistance in p53 mutant colon cancer cells by targeting the mammalian target of rapamycin[J ] . Exp Cell Res, 2017, 360(2): 328-336. DOI: 10.1016/j.yexcr.2017.09.023.

周浩泽, 李梦玮, 徐寒梅.长链非编码RNA参与肿瘤耐药机制的研究进展[J].药物生物技术, 2018, 25(1): 75-80.

ZHOU H Z, LI M W, XU H M. Recent progress in molecular mechanism of tumor drug resistance regulated by long non-coding RNA[J]. Pharm Biotechnol, 2018, 25(1): 75-80.

PENG P, ZHENG Q. Long non-coding RNA Linc00525 as a prognostic factor to regulate proliferation and apoptosis in colorectalcancer[J]. J Clin Oncol, 2019, 37(15_suppl): e15085. DOI: 10.1200/jco.2019.37.15_suppl.e15085.

GUO B, LIU L Y, YAO J Y, et al . miR-338-3p suppresses gastric cancer progression through a PTEN-AKT axis by targeting P-REX2a[J ] . Mol Cancer Res, 2014, 12(3): 313-321. DOI: 10.1158/1541-7786.MCR-13-0507.

XU H T, ZHAO L, FANG Q J, et al . MiR-338-3p inhibits hepatocarcinoma cells and sensitizes these cells to sorafenib by targeting hypoxia-induced factor 1α[J ] . PLoS ONE, 2014, 9(12): e115565. DOI: 10.1371/journal.pone.0115565.

NIU Q, LIU Z H, GAO J, et al . MiR-338-3p enhances ovarian cancer cell sensitivity tocisplatin by downregulating WNT2B[J ] . Yonsei Med J, 2019, 60(12): 1146-1156. DOI: 10.3349/ymj.2019.60.12.1146.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

下调Notch3表达对骨肉瘤细胞生物学特性的影响

TCEAL7基因对结直肠癌Caco2细胞的增殖、迁移、侵袭及凋亡的影响

SOX15基因对Caco2结肠癌细胞增殖、凋亡及迁移侵袭的影响

MiR-616在骨肉瘤中的表达及对其细胞增殖、凋亡、迁移侵袭的作用

β-arrestin1在口腔鳞状细胞癌中的表达及其对细胞增殖、迁移、侵袭的作用