吉西他滨
胰腺癌
基因敲除
PVT1型
自噬
癌症研究
化学
小RNA
转染
下调和上调
癌症
生物
医学
内科学
细胞凋亡
长非编码RNA
生物化学
基因
作者
Yunfei Liu,Dong Luo,Xia Li,Zhiqiang Li,Yu Xiao,Hongwei Zhu
出处
期刊:Pancreas
[Ovid Technologies (Wolters Kluwer)]
日期:2021-02-01
卷期号:50 (2): 227-234
被引量:29
标识
DOI:10.1097/mpa.0000000000001747
摘要
Objectives Elucidation of the regulatory mechanisms of gemcitabine sensitivity is needed to improve the therapeutic effects of this drug in pancreatic cancer. Methods PANC-1 cells were transfected with small hairpin RNA against PVT1 or microRNA (miR)-143 mimics or inhibitor. The gemcitabine sensitivity of pancreatic cancer was evaluated. Autophagosomes were analyzed with an immunofluorescence assay. Cell viability and proliferation were examined with MTT assays. Quantitative reverse transcription–polymerase chain reaction and Western blotting were used to analyze the expression of PVT1, miR-143, HIF-1α, VMP1, LC3I/II, p62, and Beclin-1. The interactions of PVT1/miR-143 and miR-143/HIF-1α were assessed by dual-luciferase reporter assays. Results PVT1 was upregulated while miR-143 was downregulated in pancreatic cancer. Both PVT1 knockdown and miR-143 overexpression suppressed autophagy and improved gemcitabine sensitivity in pancreatic cancer. PVT1 directly sponged miR-143 to regulate HIF-1α expression. MiR-143 inhibitor reversed the effect of PVT1 knockdown on autophagy and gemcitabine sensitivity. Conclusions PVT1 knockdown inhibited autophagy and improved gemcitabine sensitivity via the miR-143/HIF-1α/VMP1 axis in pancreatic cancer. Our investigation elucidated a novel regulatory mechanism of gemcitabine sensitivity and may contribute to improve the therapeutic effects of chemotherapy drugs on pancreatic cancer.
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