miR-106b Promotes Metastasis of Early Gastric Cancer by Targeting ALEX1 in Vitro and in Vivo.

Abstract

BACKGROUND/AIMS:

Aberrant expression of miR-106b is a specific symptom of many solid carcinomas. Overexpression of miR-106b has been observed in gastric cancer. The effect of miR-106b on gastric cancer has been investigated in different cell culture models. However, the effect of miR-106b on metastasis of early gastric cancer (EGC) remains unknown.

METHODS:

In the study, qRT-PCR, FISH, western blot, luciferase reporter assay, migration and invasion assays, flow cytometry and TUNEL staining were used to investigate the effect of miR-106b on metastasis of EGC.

RESULTS:

To explore the function of miR-106b in EGC, we investigated the downstream signaling of miR-106b and found that ALEX1 was a direct target of miR-106 in gastric cancer cells. Up-regulation of ALEX1 effectively rescued the cell apoptosis induced by miR-106b inhibitor and promoted the expression levels of phosphorylation of JAK1 and STAT3. Moreover, overexpression of JAK1 reduced the cell apoptosis induced by miR-106b inhibitor and decreased the expression levels of the apoptotic proteins in gastric cancer cells. Furthermore, down-regulation of miR-106b promoted apoptosis of gastric cancer cells via inhibiting JAK1/STAT3 signaling pathway in vitro and in vivo. In addition, GLPG0643, a JAK1 inhibitor, enhanced the inhibitory effect of miR-106b inhibitor on gastric cancer growth in vivo.

CONCLUSION:

These findings provided a potential therapeutic manner for the treatment of metastasis of EGC in clinic.

• Authors: Zhenglun Zhu, Qiumeng Yang, Benyan Zhang, Wei Wu, Fei Yuan, Zhenggang Zhu
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 52 Issue 3 Pg. 606-616 ( 2019) ISSN: 1421-9778 [Electronic] Germany
• PMID: 30907988 (Publication Type: Journal Article)
• Copyright: © Copyright by the Author(s). Published by Cell Physiol Biochem Press.

Chemical References

• ARMCX1 protein, human
• Antagomirs
• Armadillo Domain Proteins
• MIRN106 microRNA, human
• MicroRNAs
• Oncogene Proteins
• Protein Kinase Inhibitors
• STAT3 Transcription Factor
• Janus Kinase 1

Topics

• Animals
• Antagomirs (metabolism)
• Apoptosis
• Armadillo Domain Proteins (chemistry, genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Down-Regulation
• Humans
• Janus Kinase 1 (antagonists & inhibitors, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Neoplasm Metastasis
• Oncogene Proteins (chemistry, genetics, metabolism)
• Protein Kinase Inhibitors (pharmacology)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Stomach Neoplasms (metabolism, pathology)
• Up-Regulation