Tumor suppressor role of miR-3622b-5p in ERBB2-positive cancer.

Mingjie Lu,Wenfang Cheng,Zebo Huang,Tongshan Wang,Yichao Zhu,Wei Zhu,Ping Liu,Huo Zhang,Mingfeng He,Ting Yan,Lan Zhang

doi:10.18632/oncotarget.14968

Mingjie Lu, Wenfang Cheng + Show 9 more

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https://doi.org/10.18632/oncotarget.14968

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Abstract

Over-expression or amplification of ERBB2 is observed in multifarious carcinomas. However, the molecular mechanism of ERBB2 downregulation in ERBB2-positive cancers remains obscure. This experiment investigated the suppressive role of miR-3622b-5p in ERBB2-positive breast and gastric cancers. The luciferase activity of ERBB2 3′-untranslated region-based reporters constructed in HEK-293T, SK-BR-3 and MCF-10A cells suggested that ERBB2 was the target gene of miR-3622b-5p. Over-expressed miR-3622b-5p reduced the protein level of ERBB2, weakened the activation of mTORC1/S6, and induced the apoptosis of ERBB2-positive cancer cells. MiR-3622b-5p was significantly down-regulated in breast and gastric cancer tissues. This down-regulation in ERBB2-positive breast and gastric cancer tissues was more obvious than that in ERBB2-negative breast and gastric cancer tissues. MiR-3622b-5p turned ERBB2-positive cancer cells more vulnerable to the apoptosis induced by cisplatin and 5-fluorouracil. Taken together, miR-3622b-5p is involved in the proliferation and apoptosis of human ERBB2-positive cancer cells via targeting ERBB2/mTORC1 signaling pathway.

Highlights

Over-expression of human epidermal growth factor receptor 2 (ERBB2 or Her2) contributes to the malignant progression of tumors [1], especially the tumors of colon, bladder, ovary, endometrium, lung, uterine cervix, head and neck, and stomach [2,3,4,5,6,7,8]
MiR-3622b-5p turned ERBB2-positive cancer cells more vulnerable to the apoptosis induced by cisplatin and 5-fluorouracil
The specific mechanism of miRNA in ERBB2-positive cancers is still unknown. This experiment demonstrated for the first time that the level of miR-3622b-5p was inversely correlated with the level of ERBB2 expression in human ERBB2-positive tumors, and that miR-3622b-5p induced the apoptosis of breast www.impactjournals.com/oncotarget and gastric cancer cells by repressing ERBB2 expression

Summary

Introduction

Over-expression of human epidermal growth factor receptor 2 (ERBB2 or Her2) contributes to the malignant progression of tumors [1], especially the tumors of colon, bladder, ovary, endometrium, lung, uterine cervix, head and neck, and stomach [2,3,4,5,6,7,8]. As a molecular abnormality triggered by gene amplification, ERBB2 over-expression occurs in about 25 % of breast carcinomas and a subset of aggressive tumors [9]. The specific mechanism of miRNA in ERBB2-positive cancers is still unknown. This experiment demonstrated for the first time that the level of miR-3622b-5p was inversely correlated with the level of ERBB2 expression in human ERBB2-positive tumors, and that miR-3622b-5p induced the apoptosis of breast www.impactjournals.com/oncotarget and gastric cancer cells by repressing ERBB2 expression. MiR-3622b-5p made ERBB2-positive cancer cells more susceptible to the apoptosis induced by cisplatin and 5-fluorouracil. These findings conclude that miR-3622b-5p is a regulator of ERBB2 in ERBB2positive cancers

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