MicroRNA-362 induces cell proliferation and apoptosis resistance in gastric cancer by activation of NF-κB signalingReportar como inadecuado

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Journal of Translational Medicine

, 12:33

Cell, tissue and gene therapy


BackgroundAccording to cancer-related microRNA miRNA expression microarray research available in public databases, miR-362 expression is elevated in gastric cancer. However, the expression and biological role of miR-362 in gastric progression remain unclear.

MethodsmiR-362 expression levels in gastric cancer tissues and cell lines were determined using real-time PCR. The roles of miR-362, in promoting gastric cancer cell proliferation and apoptosis resistance, were assessed by different biological assays, such as colony assay, flow cytometry and TUNEL assay. The effect of miR-362 on NF-κB activation was investigated using the luciferase reporter assay, fluorescent immunostaining.

ResultsMiR-362 overexpression induced cell proliferation, colony formation, and resistance to cisplatin-induced apoptosis in BGC-823 and SGC-7901 gastric cancer cells. MiR-362 increased NF-κB activity and relative mRNA expression of NF-κB–regulated genes, and induced nuclear translocation of p65. Expression of the tumor suppressor CYLD was inhibited by miR-362 in gastric cancer cells; miR-362 levels were inversely correlated with CYLD expression in gastric cancer tissue. MiR-362 downregulated CYLD expression by binding its 3′ untranslated region. NF-κB activation was mechanistically associated with siRNA-mediated downregulation of CYLD. MiR-362 inhibitor reversed all the effects of miR-362.

ConclusionThe results suggest that miR-362 plays an important role in repressing the tumor suppressor CYLD and present a novel mechanism of miRNA-mediated NF-κB activation in gastric cancer.

KeywordsmiR-362 NF-κB CYLD Gastric cancer Proliferation Apoptosis AbbreviationsCYLDCylindromatosis

NF-κBNuclear factor κB

Bcl2l1BCL2-like 1

Cox-2Cytochrome c oxidase subunit II

IL-8Interleukin 8

TNFTumor necrosis factor

XIAPX-linked inhibitor of apoptosis

FLIPFLICE-inhibitory protein.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-12-33 contains supplementary material, which is available to authorized users.

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Autor: Jin-tang Xia - Lian-zhou Chen - Wei-hua Jian - Ke-Bing Wang - Yong-zhen Yang - Wei-ling He - Yu-long He - De Chen - Wen L

Fuente: https://link.springer.com/

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