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Cell Physiol Biochem. 2017;42(6):2364-2376. doi: 10.1159/000480028. Epub 2017 Aug 18.

Long Noncoding RNA H19/miR-675 Axis Promotes Gastric Cancer via FADD/Caspase 8/Caspase 3 Signaling Pathway.

Yan J1,2, Zhang Y1,2, She Q2,3, Li X1,2, Peng L1,2, Wang X3,4, Liu S2,5, Shen X1,2, Zhang W1,2, Dong Y1,2, Lu J2, Zhang G1,2.

Author information

1
Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
2
The First Clinical Medical College, Nanjing Medical University, Nanjing, China.
3
Department of Gastroenterology, The First Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
4
Department of Gastroenterology, the No, 2 Hospital of Changzhou, Changzhou, China.
5
Department of Gastroenterology, the No, 1 People's Hospital of Xuzhou, Xuzhou, China.

Abstract

BACKGROUND:

Long noncoding RNA (lncRNA) H19 is emerging as a vital regulatory molecule in the progression of different types of cancer and miR-675 is reported to be embedded in H19's first exon. However, their function and specific mechanisms of action have not been fully elucidated. The aim of this study was to identify a novel lncRNA-microRNA-mRNA functional network in gastric cancer.

METHODS:

Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the relative expression of H19 and miR-675 in normal (GES-1) and gastric cancer cell lines (SGC-7901, SGC-7901/DDP) as well as in tumor tissues. Gain and loss of function approaches were carried out to investigate the potential roles of H19/miR-675 in cell proliferation and apoptosis. Moreover, Fas associated via death domain (FADD) was validated to be the target of miR-675 via luciferase reporter assay. Western blotting was used to evaluate the protein expression of related signaling pathway.

RESULTS:

In our study H19 and miR-675 were increased in gastric cancer cell lines and tissues. Overexpression of H19 and miR-675 promoted cell proliferation and inhibited cell apoptosis, whereas knockdown of H19 and miR-675 inhibited these effects. By further examining the underlying mechanism, we showed that H19/miR-675 axis inhibited expression of FADD. FADD downregulation subsequently inhibited the caspase cleavage cascades including caspase 8 and caspase 3.

CONCLUSION:

Taken together, our results point to a novel regulatory pathway H19/miR-675/ FADD/caspase 8/caspase 3 in gastric cancer which may be potential target for cancer therapy.

KEYWORDS:

Caspase 3; Caspase 8; FADD; Gastric cancer; H19; miR-675

PMID:
28848149
DOI:
10.1159/000480028
[Indexed for MEDLINE]
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