外泌体传递lncRNA RPL23AP82促进胰腺导管腺癌吉西他滨耐药

孙运鹏; 吴欢欢; 庄磊; 陈浩然; 徐博; 黄侠鸣

doi:10.14188/j.1671-8852.2023.0508

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外泌体传递lncRNA RPL23AP82促进胰腺导管腺癌吉西他滨耐药

基础医学研究 | 更新时间：2026-11-05

- 外泌体传递lncRNA RPL23AP82促进胰腺导管腺癌吉西他滨耐药
- Exosomal delivery of lncRNA RPL23AP82 promotes gemcitabine resistance in pancreatic ductal adenocarcinoma
- 武汉大学学报（医学版） 2025年46卷第7期页码：850-856
- 作者机构：
  
  1.温州医科大学附属第一医院，肝胆胰外科，浙江温州 325000
  2.温州医科大学附属第一医院，麻醉复苏室，浙江温州 325000
  3.温州医科大学第一临床学院新医科班浙江温州 325000
- 作者简介：
  
  孙运鹏，男，1981—，医学博士，副主任医师，主要从事肝胆胰外科疾病研究, E‑mail：15967781930@163.com
- 基金信息：
  
  浙江省医药卫生科技计划项目(2020KY636)
- DOI：10.14188/j.1671-8852.2023.0508
  中图分类号： R735.9
- 收稿：2023-09-18，
  
  纸质出版：2025-07-25
- 稿件说明：
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孙运鹏,吴欢欢,庄磊等.外泌体传递lncRNA RPL23AP82促进胰腺导管腺癌吉西他滨耐药[J].武汉大学学报（医学版）,2025,46(07):850-856.

SUN Yunpeng,WU Huanhuan,ZHUANG Lei,et al.Exosomal delivery of lncRNA RPL23AP82 promotes gemcitabine resistance in pancreatic ductal adenocarcinoma[J].Medical Journal of Wuhan University,2025,46(07):850-856.
孙运鹏,吴欢欢,庄磊等.外泌体传递lncRNA RPL23AP82促进胰腺导管腺癌吉西他滨耐药[J].武汉大学学报（医学版）,2025,46(07):850-856. DOI： 10.14188/j.1671-8852.2023.0508.

SUN Yunpeng,WU Huanhuan,ZHUANG Lei,et al.Exosomal delivery of lncRNA RPL23AP82 promotes gemcitabine resistance in pancreatic ductal adenocarcinoma[J].Medical Journal of Wuhan University,2025,46(07):850-856. DOI： 10.14188/j.1671-8852.2023.0508.

摘要

目的

探究外泌体传递lncRNA RPL23AP82促进胰腺导管腺癌（PDAC）吉西他滨（GEM）耐药。

方法

（1）构建lncRNA RPL23AP82过表达载体并转染至SW1990细胞中后用GEM进行干扰、分组，对比细胞增殖活性、细胞凋亡。（2）SW1990细胞系转染shRNA‑RPL23AP82并分组，对比miR‑129、PFTK1 mRNA与PFTK1蛋白表达；SW1990细胞系转染miR‑129 mimics或miR‑129 inhibitor，对比PFTK1 mRNA、PFTK1蛋白表达。（3）SW1990细胞系诱导构建GEM耐受型PDAC细胞（SW1990‑GR）并提取外泌体与亲本细胞孵育，分别根据加入GEM、转染sh‑NC或sh‑RPL23AP82、转染sh‑NC或外泌体抑制剂GW4869，对比lncRNA RPL23AP82表达、GEM敏感性变化、细胞凋亡、细胞增殖活性。

结果

（1）对比LV‑NC组，LV‑RPL23AP82组RPL23AP82相对表达量、细胞增殖活性更高且细胞凋亡更低，LV‑NC+GEM组细胞增殖活性更低，LV‑RPL23AP82+GEM组细胞增殖活性低于LV‑RPL23AP82组（均

0.05）。（2）sh‑RPL23AP82组中RPL23AP82相对表达量低于sh‑NC组，对比sh‑NC组，sh‑RPL23AP82组miR‑129表达升高且PFTK1 mRNA、PFTK1蛋白均下降（均

0.05）；对比NC mimics组，miR‑129 mimics组miR‑129表达升高且miR‑129 inhibitor组miR‑129表达降低，miR‑129 mimics组PFTK1 mRNA和PFTK1蛋白水平降低，而miR‑129 inhibitor组PFTK1 mRNA和PFTK1蛋白水平升高（均

0.05）。（3）SW1990‑GR组lncRNA RPL23AP82表达、SW1990‑GR组细胞增殖活性升高，对比SW1990‑GR组，SW1990‑GR+GEM组细胞增殖活性下调且细胞凋亡升高，耐药细胞SW1990‑GR与GEM共干扰后细胞凋亡下降（均

0.05）；敲低RPL23AP82后细胞增殖活性下调；GW4869抑制外泌体分泌后GW4869降低，抑制细胞增殖活性；抑制剂GW4869处理细胞增殖活性下降，细胞凋亡上升（均

0.05）。

结论

外泌体上调lncRNA RPL23AP82可降低miR‑129表达并通过刺激PFTK1表达促进吉西他滨耐药。

Abstract

Objective

To probe exosomal delivery of lncRNA RPL23AP82 to promote gemcitabine (GEM) resistance in pancreatic ductal adenocarcinoma (PDAC).

Methods

(1) The lncRNA RPL23AP82 overexpression vector was constructed and transfected into SW1990 cells

after which they were interfered with and grouped with GEM to compare their proliferative activity and apoptosis. (2) SW1990 cell lines were transfected with shRNA⁃RPL23AP82 and grouped to compare miR⁃129

PFTK1 mRNA with PFTK1 protein expression; SW1990 cell lines were transfected with miR⁃129 mimics or miR⁃129 inhibitor

comparing PFTK1 mRNA

PFTK1 protein expression. (3) SW1990 cell line was induced to construct GEM‑resistant PDAC cells (SW1990‑GR) and exosomes were extracted and incubated with the parental PDAC cells. According to the addition of GEM

transfection with sh‑NC or sh‑RPL23AP82

transfection with sh‑NC or exosome inhibitor GW4869

the patients were divided into groups. The lncRNA RPL23AP82 expression

GEM sensitivity

cell apoptosis and cell proliferation activity were compared.

Results

(1) Compared with the LV⁃NC group

the relative expression of RPL23AP82

cell proliferation activity

and apoptosis were higher and lower in the LV⁃RPL23AP82 group

cell proliferation activity was lower in the LV⁃NC+GEM group

and cell proliferation activity was higher in the LV⁃RPL23AP82+GEM group than in the LV⁃RPL23AP82 group (all

0.05). RPL23AP82+GEM group had lower cell proliferation activity than the LV⁃RPL23AP82 group (all

0.05). (2) The relative expression of RPL23AP82 in the sh⁃RPL23AP82 group was lower than that in the sh⁃NC group; comparing with the sh⁃NC group

miR⁃129 expression was elevated in the sh⁃RPL23AP82 group and PFTK1 mRNA and PFTK1 protein were decreased (both

0.05); compared with the NC mimics group

miR⁃129 expression was elevated in the miR⁃129 mimics group and decreased in the miR⁃129 inhibitor group

and miR⁃129 expression was increased in the sh⁃NC group

and miR⁃129 expression was decreased in the sh⁃NC group

and miR⁃129 expression was increased in the sh⁃NC group. The miR⁃129 expression was decreased in the miR⁃129 mimics group

and PFTK1 mRNA and PFTK1 protein levels were decreased in the miR⁃129 mimics group

while PFTK1 mRNA and PFTK1 protein levels were increased in the miR⁃129 inhibitor group (both

0.05). (3) The expression of lncRNA RPL23AP82 in the SW1990⁃GR group and cell proliferative activity was elevated in the SW1990⁃GR group

com

pared with the SW1990⁃GR group

cell proliferative activity was down⁃regulated in the SW1990⁃GR+GEM group and apoptosis was elevated

apoptosis decreased after co⁃disturbance of SW1990⁃GR and GEM in drug⁃resistant cells (both

0.05); cell proliferative activity was down⁃regulated after knockdown of RPL23AP82; GW4869 inhibition of exosome secretion decreased after GW4869 inhibition and inhibited cell proliferative activity; proliferative activity of inhibitor GW4869⁃treated cells decreased and apoptosis rose (both

0.05).

Conclusion

Exosomal upregulation of lncRNA RPL23AP82 reduces miR⁃129 expression and promotes gemcitabine resistance by stimulating PFTK1 expression.

关键词

Keywords

references

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