Long Noncoding RNA HCP5 Regulates Pancreatic Cancer Gemcitabine (GEM) Resistance By Sponging Hsa-miR-214-3p To Target HDGF
Long Noncoding RNA HCP5 Regulates Pancreatic Cancer Gemcitabine (GEM) Resistance By Sponging Hsa-miR-214-3p To Target HDGF
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DOI：
10.2147/ott.s222703
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Yu, Xiao
中科院分区：
文献类型：
--
作者：
Liu, Yunfei;Wang, Jiale;Yu, Xiao
背景：吉西他滨（GEM）是治疗原发性肝癌最常用的化疗药物之一。然而，化疗耐药总是在治疗一段时间后发生，表明预后不良。lncRNA可能在PC中起重要作用，并可作为PC耐药的预后生物标志物。本研究旨在探讨lncRNA HCP5在PC中的作用。材料与方法：采用QRT-PCR方法检测lncRNA HCP5在PC中的表达。在GEM抗性PC细胞中研究了敲低lncRNA HCP 5对增殖、迁移、侵袭、细胞凋亡和自噬的影响。通过生物信息学分析、荧光素酶报告基因分析和RNA免疫沉淀分析，预测与lncRNA HCP5相互作用的miRNAs和与miR-214 - 3p相互作用的miRNAs。结果：lncRNA HCP5在PC组织中表达上调，尤其在耐药PC组织和耐药PC细胞中表达上调。伤口愈合、Transwell实验、流式细胞术、Western blot、荧光素酶报告基因实验和RNA免疫沉淀（RIP）实验结果表明，lncRNA HCP 5作为ceRNA通过miR-214 - 3p靶向HDGF，调控GEM耐药PC细胞的增殖、侵袭、迁移、细胞凋亡和自噬。我们的研究结果表明，lncRNA HCP 5在HCC中高度表达，并且GEM抗性PC细胞的发展涉及增殖、侵袭、迁移，细胞凋亡和自噬通过miR-214 - 3p/HDGF轴。靶向lncRNA HCP 5可以改善基于吉西他滨的治疗效果。
Background: Gemcitabine (GEM) is one of the most widely chemotherapy drugs in PC. However, the chemotherapy resistance always occurs after a period of treatment indicating poor prognosis. lncRNA may play an essential role in PC and serve as a prognosis biomarkers in PC with GEM-resistance. In our study, we aim to investigate the role of lncRNA HCP5 in PC.Materials and methods: QRT-PCR detected the expression of lncRNA HCP5. The effects of knockdown lncRNA HCP5 on the proliferation, migration, invasion, cell apoptosis and autophagy were investigated in GEM-resistance PC cells. Bioinformatic analysis, luciferase reporter assay and RNA immunoprecipitation assay were performed to predict for potential miRNAs that can interact with lncRNA HCP5 and mRNAs that can interact with miR-214-3p.Results: Our study revealed that lncRNA HCP5 expression was upregulated in PC tissues, especially increased expression in GEM-resistant PC tissues and GEM-resistant PC cells. Wound healing, Transwell assays, flow cytometry, Western blot, luciferase reporter assay and RNA immunoprecipitation (RIP) results demonstrated lncRNA HCP5 acted as a ceRNA to regulate GEM-resistance PC cells' proliferation, invasion, migration, cell apoptosis and autophagy by targeting HDGF via miR-214-3p.Conclusion: Our results revealed that lncRNA HCP5 is highly expressed in HCC, and development of GEM-resistance PC cells involving the processes of proliferation, invasive, migration, cell apoptosis and autophagy through the miR-214-3p/HDGF axis. Targeting lncRNA HCP5 may improve gemcitabine-based therapeutic efficacy.