Decreased expression of miR-939 contributes to chemoresistance and metastasis of gastric cancer via dysregulation of SLC34A2 and Raf-MEK-ERK pathwayReportar como inadecuado

Decreased expression of miR-939 contributes to chemoresistance and metastasis of gastric cancer via dysregulation of SLC34A2 and Raf-MEK-ERK pathway - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Molecular Cancer

, 16:18

First Online: 23 January 2017Received: 12 August 2016Accepted: 09 January 2017DOI: 10.1186-s12943-017-0586-y

Cite this article as: Zhang, JX., Xu, Y., Gao, Y. et al. Mol Cancer 2017 16: 18. doi:10.1186-s12943-017-0586-y


BackgroundThe development of chemoresistance and metastasis are the leading causes of death for gastric cancer GC patients, however, the molecular mechanisms involved remain unclear. Dysregulation of miRNAs is associated with a variety of disease, including GC. Recently, microarray profiling analysis revealed that miR-939 was dysregulated in human GC samples, but the role of miR-939 in GC has not been intensively investigated.

MethodsIn the present study, we firstly examined the expression pattern of miR-939 in two independent cohorts of clinical GC samples: one cohort of 112 GC patients with stage I-III disease who underwent surgery followed by adjuvant chemotherapy; and another cohort of 110 GC patients with stage IV disease who received palliative chemotherapy. A series of in vivo and in vitro assays were then performed to investigate the function of miR-939 in GC.

ResultsWe detected that reduced expression of miR-939 was associated with chemoresistance and increased risk of tumor recurrence in GC patients. Further function study demonstrated that overexpression of miR-939 suppressed GC cell growth, and enhanced 5-fluorouracil-induced chemosensitivity by compromising cellular growth and inducing apoptosis in vitro and in vivo. Moreover, miR-939 repressed the migration and invasion of GC cells in vitro, and diminished the occurrence of lung metastasis in vivo. We further identified solute carrier family 34 member 2 SLC34A2 was a novel target of miR-939. Mechanistically, we elucidated that miR-939 exerted its function mainly through inhibiting SLC34A2-Raf-MEK-ERK pathway, which is activated in GC. Multivariate analysis identified miR-939, SLC34A2, and their combination as independent indicators for poor prognosis and tumor recurrence in GC patients.

ConclusionOur data indicate that miR-939 acts as a tumor suppressor miRNA in GC, and miR-939-SLC34A2 axis represents a novel therapeutic strategy for future GC treatment.

KeywordsmiR-939 SLC34A2 Gastric cancer Chemoresistance Metastasis Abbreviations5-Fu5-fluorouracil

AUCArea under the curve

CRComplete response

FFPEFormalin-fixed paraffin-embedded

GCGastric cancer


NCNo change

OSOverall survival

PDProgressive disease

PRPartial response

ROCReceiver operating characteristic

TTRTime to recurrence

Electronic supplementary materialThe online version of this article doi:10.1186-s12943-017-0586-y contains supplementary material, which is available to authorized users.

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Autor: Jia-Xing Zhang - Yi Xu - Ying Gao - Cui Chen - Zhou-San Zheng - Miao Yun - Hui-Wen Weng - Dan Xie - Sheng Ye


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