Team:Worldshaper-Wuhan/Description
Introduction
Limitation
Importance
microRNA Biomarkers
LncRNAs
References
Introduction
Breast Cancer: one of the most common cancers in the world
Breast cancer, a type of cancer that develops from breast tissue, is a global health concern[1]. In fact, breast cancer is the most common cancer among women and is the second cancer frequently occurring worldwide of newly-diagnosed cancers(Fig 1). Breast cancer remains the leading cancer-related cause of disease burden for women, affecting one in 20 globally and as many as one in eight in high-income countries.
Breast cancer occurs when some breast cells begin to grow abnormally. These cells divide more rapidly than healthy cells do and continue to accumulate, forming a lump or mass[2]. Cells may spread (metastasize) through the patient's breast to the lymph nodes or to other parts of the body, resulting in its high incidence and death rate[3](Fig 1 and 2). Clinically, breast cancers are characterized into three basic types based on their immunohistochemical properties. They are triple-negative breast cancer, estrogen receptor (ER) and progesterone receptor (PR)-positive-HR positive breast cancer, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer[4].
Figure 1. The incidence of the most common cancers among females worldwide in 2018.
Figure 2. The mortality of the most common cancers among females worldwide in 2018.
The Limitation of Current Breast Cancer Detection Methods
The poor prognosis of most breast cancer patients is due to late diagnosis. The most critical point for best prognosis is to identify early-stage cancer cells[5]. Choosing the better techniques to diagnose the stage of breast cancer for further control is the paramount task. Investigators have studied many breast diagnostic approaches (Table 1), but many of the techniques have their limitations such as being expensive, time consuming and not suitable for young women [6]. Thus, it is urgent for us to discover a new way to detect breast cancer, which is also available to most of the people. This way, people may be able to detect breast cancer earlier and have a higher possibility to be healed.
Table 1. Techniques used for diagnosis of breast cancer
The Important of Biomarkers for Chemoresistance and Radioresistance
The chemotherapy and radiotherapy are the common methods for treating breast cancer. One major obstacle in cancer treatment is resistance of cancer cells to anticancer drug therapies and radiotherapy[7]. In fact, drug resistance and radio resistance are currently the most common factor in tumor recurrence. Therefore, new biomarkers need to be identified to help doctors to evaluate the effect of chemotherapy and radiotherapy and select these alternate treatments[8].
Therefore, our team is committed to design a new method based on new biomarkers that can diagnose breast cancer and evaluate the effect of chemotherapy and radiotherapy with specificity, accuracy and ease, which also has the potential to be used in cancer treatment in the future.
microRNA Biomarkers for Diagnosis and Chemoresistance/radioresistance
Non-coding RNAs (ncRNAs) are ribonucleic acid (RNA) molecules that are not translated into protein products. The ncRNAs can be divided into two categories according to length: one category is small ncRNAs (< 200 bp), including microRNA, and the other one is long non-coding RNAs (lncRNAs) (>200 bp)[9]. miRNAs’ levels often been reported to be altered in breast cancer patients and have being discovered in body fluids (serum, plasma and others)[10] . Recently, miR-155 is reported to have high sensitivity and specificity in identifying breast cancer. Moreover, the expression of miR-155 is closely related to the chemoresistance and radioresistance in breast cancer patients[11]. That has inspired us to use the miR-155 as the new biomarker to be used in diagnosing breast cancer and evaluating the effect of chemotherapy and radiotherapy in breast cancer patients.
LncRNAs Act as Sponges to Compete miRNAs in Breast Cancer
Long noncoding RNAs (lncRNAs) are defined as transcripts longer than 200nucleotides that lack an extended open reading frame and thus do not code for proteins. Comprehensive study of the human genome have identified over 8,000 lncRNAs. lncRNAs play an important role in a variety of physiological processes, including epigenetic regulation of gene expression, RNA decay, microRNA regulation, RNA splicing, protein folding[12]. Studies have revealed a broad spectrum of lncRNAs that are involved in a variety of disease, including tumor progression. In breast cancer research, several lncRNAs are identified as tumor driving oncogenic lncRNAs and some are identified as tumor suppressive lncRNAs. They are involved in apoptosis, cell growth, cell migration and invasiveness[13]. Recently, several studies indicated that lncRNAs could act as sponges to compete miRNAs. miRNA Sponges contain complementary binding sites to a miRNA of interest, which inhibit miRNA activity [14]. Currently, miRNA Sponges served as inhibitors for many miRNA in researches [15]. When perfectly matched, RNA sponge site will bind to the target miRNA preventing it from binding to their target mRNAs and to perform mRNA silencing. This mechanism gives rise to our idea of fusing a sponge RNA with binding sites complementary to the sequence of miR-155 to a plasmid that has reporter gene, EGFP-C1 for instance, which will monitor the expression of miR-155 in the cells.
References:
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