Abstract

BackgroundThe role of TMED3 involved in cancers has been seldom described, let alone in breast cancer. To explore the clinicopathological significance of TMED3 expression and the biological roles involved in breast cancer cells, we undertook the study.MethodsImmunohistochemistry was performed to observe the pattern of TMED3 expression in breast cancer tissues, totaling 224 cases; followed by detailed statistical analysis between TMED3 expression versus clinicopathological information available. To explore the role of TMED3 involved in the malignant behaviors of breast cancer cells, wound-healing and Transwell assays were conducted to evaluate the variation of migration and invasion of MCF-7 and MDA-MB-231 cells whose TMED3 has been stably silenced using lenti-viral based short hairpin RNA (shRNA) vectors. MTT, clonogenic assay and xenograft nude mice model were undertaken to observe the variation of proliferation both in vitro and in vivo.ResultsIt was shown that elevated TMED3 markedly correlated with ER, PR, Her-2 status, and lymph nodes metastases in addition to significant association with poor overall prognosis. In vitro, TMED3 was shown to promote proliferation, migration and invasion of breast cancer cells. Moreover, miR-188-3p was identified as a novel negative regulator of TMED3 in breast cancer, which can slow down the proliferation, migration and invasion of MCF-7 cells. Results from in vivo xenograft nude mice models showed that lenti-viral based miR-188-3p re-expression can markedly impair the tumor growth.ConclusionsOur data define and bolster the oncogenic role of TMED3 in breast cancer.

Highlights

  • The role of TMED3 involved in cancers has been seldom described, let alone in breast cancer

  • Up‐regulated TMED3 remarkably correlated with poor overall survival in breast cancer To learn about the expression pattern of TMED3 in breast cancer tissues, immunohistochemistry (IHC) was carried out on tissue microarray consisting of 112 cases breast cancer tissue dots

  • IHC detection revealed the highly heterogenous expression of TMED3, with the immunostaining varying from case to case from being negative, weak, and moderate to strong positive in breast cancer tissues (Fig. 1a–d)

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Summary

Introduction

The role of TMED3 involved in cancers has been seldom described, let alone in breast cancer. To explore the clinicopathological significance of TMED3 expression and the biological roles involved in breast cancer cells, we undertook the study. In China, the burden of female breast cancer is getting increasingly severe, especially in urban areas of. Despite the great advancement in the understanding, surgical and meditations; breast cancer remains to be a major cause of death worldwide [3]. Further investigation of novel oncogenes involved in the pathogenesis of breast cancer is needed and necessary. The ten members of TMED family have been discovered [5]; many TMED proteins [6–9] have been investigated and reported except for TMED3 which has been comparatively seldom described in the context of

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