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Introduction
Breast cancer has become a leading cause of cancer-associated mortality in the world, and the most common cancer among women (1). The majority of these mortalities are caused by distant metastasis and resistance to the currently available therapeutics (2). An estimated 15-20% of patients with breast cancer exhibit overexpression of human epidermal growth factor receptor 2 (HER2), leading to a poorer prognosis and survival (3,4). At present, therapy with anti-HER2 mono-antibodies, including trastuzumab, is applied to treat patients with HER2-positive breast cancer (5,6). Trastuzumab is designed to target HER2 and silence its function, and is primarily used for early stage or metastatic gastric and breast cancer with positive HER2 mutations. Trastuzumab may be effective for initial treatment, although resistance increases substantially following a period of exposure. In addition, there is a clear need for useful therapeutic biomarkers that may be used for predicting chemoresponses to treatment with trastuzumab (7). Therefore, there is an urgent necessity to reveal the mechanism of trastuzumab resistance and identify useful molecular markers and therapeutic targets for patients with breast cancer.
With the advanced development of whole genome and transcriptome sequencing technologies and the ENCODE project (8), researchers have drawn the conclusion that the majority of genomic DNA is represented in processed transcripts that may not be translated into functional proteins, namely non-coding RNAs (ncRNAs) (9). Long ncRNAs (lncRNAs) are an important group of ncRNAs that contain >200 nucleotides (10). During recent years, numerous reports have demonstrated that lncRNAs may serve as critical biological regulators in the functions of cellular and molecular signaling pathways; for example, they may exert their important functional roles at the post-transcriptional level by sponging microRNAs (11), and mediate transcriptional regulation via chromatin modification (12,13).
Exosomes have attracted considerable attention in the field of biomarker discovery. The release of exosomes into the extracellular space affords an opportunity to exchange cellular contents, membranes, proteins and gene fragments (14). Exosomes are membrane-derived vesicles and have a size range of 20-200 nm when released into bodily fluids, including blood, urine and malignant ascites. These vesicles contain DNA, protein fragments, and coding or ncRNAs secreted by their parental cell cytoplasm, and may be absorbed into recipient cells (15). A recent study indicated that the exosomes from chemosensitive/resistant cells were able...