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上调的外泌体 miR-23b-3p 在胰腺癌的进展中发挥调节作用。

Upregulated exosomic miR‑23b‑3p plays regulatory roles in the progression of pancreatic cancer.

机构信息

Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.

Department of Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.

出版信息

Oncol Rep. 2017 Oct;38(4):2182-2188. doi: 10.3892/or.2017.5919. Epub 2017 Aug 24.

DOI:10.3892/or.2017.5919
PMID:28849236
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5652966/
Abstract

Pancreatic cancer (PC) is one of the most lethal malignances. Identification of biomarkers for early diagnosis of PC is a key imperative. MicroRNAs (miRNAs) have been shown to be valuable biomarkers in the context of several cancers. Exosomes refer to vesicles released by the tumor cells at the early stage of disease. Thus, detection of miRNA in exosomes can be used as a potential biomarker for PC. In this study, we profiled serum levels of miRNAs in patients with chronic pancreatitis (CP) and PC; the role of miR‑23b‑3p in PC progression was assessed in vitro. Additionally, we assessed, the expression of miR‑23b‑3p in exosomes isolated from serum samples and assessed the correlation between the expression of miR‑23b‑3p and carbohydrate antigen 19-9 (CA19-9). Three serum samples each were randomly selected from healthy controls (n=20), and patients with CP (n=18) and PC (n=16) for miRNA microarray profiling. The dysregulated miRNAs were confirmed using qRT‑PCR. Four dysregulated miRNAs common to patients with CP and PC were identified on miRNA microarray analysis and confirmed by qRT‑PCR. miR‑23b‑3p level was consistently higher in serum samples from PC patients as compared to those from healthy controls and CP patients (p<0.05). Overexpression of miR‑23b‑3p promoted proliferation, migration, and invasion capability of PC cells in vitro (p<0.05). Furthermore, miR‑23b‑3p was upregulated in exosomes of PC serum samples and the supernatant of pancreatic cancer cells (PANC‑1), and the expression levels of miR‑23b‑3p were associated with those of serum CA19-9 levels. This study provides insights into the potential role of miR‑23b‑3p as a novel biomarker and target for treatment of PC.

摘要

胰腺癌(PC)是最致命的恶性肿瘤之一。鉴定用于 PC 早期诊断的生物标志物是当务之急。在几种癌症中,miRNAs 已被证明是有价值的生物标志物。外泌体是指在疾病早期由肿瘤细胞释放的囊泡。因此,检测外泌体中的 miRNA 可以作为 PC 的潜在生物标志物。在这项研究中,我们对慢性胰腺炎(CP)和 PC 患者的血清 miRNA 水平进行了分析;评估了 miR-23b-3p 在 PC 进展中的作用。此外,我们评估了从血清样本中分离的外泌体中 miR-23b-3p 的表达,并评估了 miR-23b-3p 的表达与碳水化合物抗原 19-9(CA19-9)之间的相关性。随机从健康对照者(n=20)、CP 患者(n=18)和 PC 患者(n=16)中各选择 3 个血清样本进行 miRNA 微阵列分析。使用 qRT-PCR 对差异表达的 miRNA 进行了验证。miRNA 微阵列分析鉴定出 CP 和 PC 患者共有 4 个差异表达的 miRNA,并通过 qRT-PCR 进行了验证。与健康对照组和 CP 患者相比,PC 患者的血清样本中 miR-23b-3p 水平始终更高(p<0.05)。miR-23b-3p 的过表达促进了 PC 细胞在体外的增殖、迁移和侵袭能力(p<0.05)。此外,PC 患者血清样本的外泌体和胰腺癌细胞(PANC-1)的上清液中 miR-23b-3p 上调,miR-23b-3p 的表达水平与血清 CA19-9 水平相关。本研究为 miR-23b-3p 作为 PC 新型生物标志物和治疗靶点的潜在作用提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c39/5652966/37e037a18121/OR-38-04-2182-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c39/5652966/ef8cb2604f9a/OR-38-04-2182-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c39/5652966/3c4e2a45f115/OR-38-04-2182-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c39/5652966/e112e6e16645/OR-38-04-2182-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c39/5652966/5857ade6b477/OR-38-04-2182-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c39/5652966/37e037a18121/OR-38-04-2182-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c39/5652966/ef8cb2604f9a/OR-38-04-2182-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c39/5652966/3c4e2a45f115/OR-38-04-2182-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c39/5652966/e112e6e16645/OR-38-04-2182-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c39/5652966/5857ade6b477/OR-38-04-2182-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c39/5652966/37e037a18121/OR-38-04-2182-g04.jpg

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