Knockdown of TRIM47 inhibits breast cancer tumorigenesis and progression through the inactivation of PI3K/Akt pathway
Introduction
Breast cancer is a kind of cancer that develops from breast tissue and remains the leading type of cancer in women worldwide, which accounts for 25% of all cases [1]. The management of breast cancer includes surgery and adjuvant therapy depending on cancer stage and the patient's personal conditions [2]. The 5-year survival rate for locally invasive breast cancer is quite high (up to 98%) [2]. However, the 5-year survival rate for distant metastatic breast cancer is poor (approximately 26%) [2]. In the last decade, the treatment for metastatic breast cancer is largely focused on systemic therapy. Recently, target therapy becomes attractive for the breast cancer treatment [3]. Previous studies have proven that some driver pathways including mechanistic target of rapamycin (mTOR) pathway and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway have revolutionized the management of metastatic breast cancer [3]. In addition, several molecules such as human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF) receptor, and epidermal growth factor receptor (EGFR) can be used as targets for controlling the metastatic breast cancer [3]. The targetable pathways and molecules are still under investigation.
Tripartite motif (TRIM) protein family is a group of proteins belonged to RING family of ubiquitin E3 ligases, which are characterized by three conserved domains, RING, B-Box and coiled-coil (RBCC) [4]. TRIM family proteins participate in a wide range of biological processes, such as cell growth, migration, differentiation, apoptosis and immunity [[5], [6], [7]]. Tripartite motif 47 (TRIM47), a member of the TRIM family proteins, plays a key role in several types of cancers including prostate cancer, colorectal cancer and non-small cell lung cancer [[8], [9], [10]]. However, the expression and functional role of TRIM47 in breast cancer remain unclear. Therefore, we aimed to investigate whether TRIM47 can affect the progression and metastasis of breast cancer in the present study.
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Patient samples
Twenty four breast cancer tissues and adjacent normal tissues were collected from breast cancer patients who underwent surgical operations in Huaihe Hospital of Henan University (Kaifeng, China) from January 2017 to July 2018. All clinical samples were rapidly freeze in liquid nitrogen and then stored at −80 °C until use. The current study was approved by the Ethics Committee of Huaihe Hospital of Henan University. All participants were informed and have written the informed consent agreement
TRIM47 expression was elevated in human breast cancer tissues and cell lines
First, we analyzed the TRIM47 expression in human breast cancer tissues and cell lines. The results of qRT-PCR showed that the TRIM47 expression in breast cancer tissues was significantly higher than that in adjacent normal tissues (Fig. 1A). Besides, the mRNA levels of TRIM47 were also increased in breast cancer cell lines including BT-20, BT549, MCF-7 and MDA-MB-231 cells, especially in MCF-7 and MDA-MB-231 cells, when compared with the normal human breast epithelial cells MCF-10A (Fig. 1B).
Discussion
TRIM proteins often play roles in the post-translational protein modification, including ubiquitylation and other ubiquitin-like modifications, therefore, TRIM proteins are involved in various events, including oncogenesis [4,11]. One study reported that TRIM47 expression level was higher in non-small cell lung cancer tissues than in normal adjacent tissues, and overexpression of TRIM47 closely correlated with poor prognosis in patients with non-small cell lung cancer [10]. Another study showed
Author statement
No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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