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Circulating extracellular vesicle-encapsulated HULC is a potential biomarker for human pancreatic cancer.

ABSTRACT: The role of long noncoding RNAs (lncRNAs) in the epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) is unclear. Some lncRNAs can be transferred by extracellular vesicles (EVs) and have potential as biomarkers. Here, we identify an lncRNA that could serve as a biomarker for PDAC and show the functional roles of the lncRNA. Expression profiling of lncRNAs revealed that highly upregulated in liver cancer (HULC) was highly expressed, and induced, by transforming growth factor-? in PDAC cells and their EVs. Knockdown of HULC decreased PDAC cell invasion and migration by inhibiting the EMT. Thus, HULC could be transferred by EVs, and promote EMT, invasion, and migration in recipient PDAC cells. To assess the roles of HULC, PDAC cell xenografts in nude mice were established. Knockdown of HULC in PDAC cells implanted in mice inhibited tumor growth. Moreover, microRNA-133b suppressed PDAC cell invasion and migration by inhibiting the EMT through targeting HULC. Furthermore, serum samples were obtained from 20 PDAC and 22 intraductal papillary mucinous neoplasm (IPMN) patients, as well as 21 healthy individuals. Analysis of serum EV HULC expression by digital PCR showed that HULC expression was significantly increased in PDAC patients compared to healthy individuals or IPMN patients. Additionally, HULC showed good predictive performance for discriminating PDAC, suggesting that the analysis of EV-encapsulated HULC would contribute to the diagnosis for human PDAC. Extracellular vesicle-transported HULC promotes cell invasion and migration by inducing the EMT, and microRNA-133b suppresses the EMT by targeting HULC. Extracellular vesicle-encapsulated HULC could be a potential circulating biomarker for human PDAC.

SUBMITTER: Takahashi K

PROVIDER: S-EPMC6942436 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Circulating extracellular vesicle-encapsulated HULC is a potential biomarker for human pancreatic cancer.

Takahashi Kenji K Ota Yu Y Kogure Takayuki T Suzuki Yuko Y Iwamoto Hidetaka H Yamakita Keisuke K Kitano Yohei Y Fujii Satoshi S Haneda Masakazu M Patel Tushar T Ota Tsuguhito T

Cancer science 20191205 1

The role of long noncoding RNAs (lncRNAs) in the epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) is unclear. Some lncRNAs can be transferred by extracellular vesicles (EVs) and have potential as biomarkers. Here, we identify an lncRNA that could serve as a biomarker for PDAC and show the functional roles of the lncRNA. Expression profiling of lncRNAs revealed that highly upregulated in liver cancer (HULC) was highly expressed, and induced, by transforming growt ...[more]

PMID: 31715081

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Project description:Background and purposeThis study aimed to evaluate whether extracellular-vesicle-incorporated microRNAs (miRNAs) are potential biomarkers for cancer-related stroke.MethodsThis cohort study compared patients with active cancer who had embolic stroke of unknown sources (cancer-stroke group) with patients with only cancer, patients with only stroke, and healthy individuals (control groups). The expression profiles of miRNAs encapsulated in plasma exosomes and microvesicles were evaluated using microarray and validated using quantitative real-time polymerase chain reaction. The XENO-QTM miRNA assay technology was used to determine the absolute copy numbers of individual miRNAs in an external validation cohort.ResultsThis study recruited 220 patients, of which 45 had cancer-stroke, 76 were healthy controls, 39 were cancer controls, and 60 were stroke controls. Three miRNAs (miR-205-5p, miR-645, and miR-646) were specifically incorporated into microvesicles in patients with cancer-related stroke, cancer controls, and stroke controls. The area under the receiver operating characteristic curves of these three miRNAs were 0.7692-0.8510 for the differentiation of patients with cancer-stroke from cancer-controls and 0.8077-0.8846 for the differentiation of patients with cancer-stroke from stroke controls. The levels of several miRNAs were elevated in the plasma exosomes of patients with cancer, but were lower than those in plasma microvesicles. An in vivo study showed that systemic injection of miR-205-5p promoted the development of arterial thrombosis and elevation of D-dimer levels.ConclusionStroke due to cancer-related coagulopathy was associated with deregulated expression of miRNAs, particularly microvesicle-incorporated miR-205-5p, miR-645, and miR-646. Further prospective studies of extracellular-vesicle-incorporated miRNAs are required to confirm the diagnostic role of miRNAs in patients with stroke and to screen the roles of miRNAs in patients with cancer.

Dataset Information

Circulating extracellular vesicle-encapsulated HULC is a potential biomarker for human pancreatic cancer.

Publications

Circulating extracellular vesicle-encapsulated HULC is a potential biomarker for human pancreatic cancer.

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