Team:Worldshaper-Wuhan/Background
Your Custom Text Here (Figure 1. Colorectal Cancer Incidence Rate in China in 2011. )[4]
Colorectal Cancer is one of the most common cancer and one of the leading causes of cancer-related death around the world. It is a disease that forms malignant tumors in colon or rectum. Of cancers affecting both men and women, colorectal cancer is the second leading cancer killer in the United States [1]. In China, the colorectal cancer is ranked the sixth most common cancer and one of the deadliest of its kind. The overall incidence of colorectal cancer was 23.03/100,000 and grew progressively in people of advanced years [2]. In 2012, it was estimated that 149,722 people died from the cancer which made up 7.09% of the overall cancer-related death [3].
Virtually, most colorectal cancer arises from clusters of cells, called polyp, which grow in the inner linings of colon or rectum. Although only a number of, not all, colorectal polyps become cancerous over time, detecting and analyzing these polyps are key to the diagnosis and treatment of the cancer [5]. At present, available detective methods include: Sigmoidoscopy, Colonoscopy, Double-contrast Barium Enema, CT Colonoscopy, Guaiac-based fecal occult blood test, Fecal Immunochemical Test and Stool DNA Test[6]. Despite their diversity, however, none of the listed methods offers a quick and accurate detection that can be performed at little to none negative effects to the patients. For example, methods pertaining to scopes are often time-consuming and requires accommodation on diets, leaving alone the fact that they could miss small developing polyps. Sedation is also often needed to ease the discomforts during the test, which also inevitably leads to side-effects such as numbness and being unable to commute. Likewise, tests of fecal sample have chances of producing false results that can possibly hinder patients’ treatments, even though they are inexpensive and relatively easier to be performed [7].
(Figure 2. Parts of Colon)[8]
Through more improved treatment and more advanced early detection, the group of cancer survivor is growing on a consistent base. Therapeutic advancements are shown to improve the survival rate to a great extent and the current five-year survival rate of colorectal cancer in every stage is approximately 65%, which is ideal with regards that it is one of the world’s most common cancers [9]. This figure, however, shall not keep us blind from the fact that cancer survivors are subject to both long-term and short-term side-effects during and after the treatments, let alone the patients who are still undergoing treatment. These can include: nerve damage, infertility, increased risks of other cancer, cataracts, osteoporosis, lymphedema and so on. Although the extents of aftereffects vary from person to person, their significance in disturbing people’s lives should not be ignored [10].
microRNAs (miRNAs) are noncoding single strand small RNA molecules of about 22 nucleotides in length that act as post-transcriptional regulators of gene expression and control many critical cellular processes, including cancer[11]. miRNAs’ levels often been reported to be altered in cancer patients and have being discovered in body fluids (serum, plasma and others) [12]. Recently, miR-21 is reported to have high sensitivity and specificity in identifying colorectal cancer. Meanwhile, miR-21 served as a therapeutic target by targeting PTEN, PCDC4, TGFBR2 and CDC25A, all of which involved in proliferation, apoptosis, invasion and migration in colorectal cancer [13].That has inspired us to use the miR-21 as the new biomarker to be used in diagnosing and treatment colorectal cancer.
Background
![(Figure 1. Colorectal Cancer Incidence Rate in China in 2011. )[4]](https://static.igem.org/mediawiki/2017/9/94/T-Worldshaper-Wuhan-00001.jpeg)
Colorectal Cancer: one of the MOST common cancers in the world
The Limitation of Current Colorectal Cancer Detection Methods
![(Figure 2. Parts of Colon)[8]](https://static.igem.org/mediawiki/2017/8/8b/T-Worldshaper-Wuhan-00002.jpeg)
The Limitations of Treatments for Colorectal Cancer
Therefore, our team is committed to design a new model based on new biomarkers that can diagnose colorectal cancer with specificity, accuracy and ease, which also has the potential to be used in cancer treatment in the future.
What is the microRNA?
What is the miRNA Sponge?
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 research[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-21 to a plasmid that has reporter gene, EGFP-C1 for instance, which will monitor the expression of miR-21 in the cells.
Reference:
1. https://www.cdc.gov/cancer/colorectal/
2. Chen W Zheng R，Zhang S，et al_Annual report on stams of cancer in China，2010．Chin T Cancer Res 2014：26：48—58．
3. Dai Z，Zheng Rs，zou xN，et a1．Analysis and prediction of c010rectal cancer incidence trend in China．Zhonghua Yu Fang Yi Xue Za Z11i 2012 46:598—603．
4. Liu S, Zheng R, Zhang M, Zhang S, Sun X, Chen W. Incidence and mortality of colorectal cancer in China, 2011. Chin J Cancer Res. 2015 Feb;27(1):22-8.
5. Bessa X. Serrated polyps and synchronous advanced neoplasia in average-risk persons. Gastroenterol Hepatol (N Y). 2014 Mar;10(3):190-2.
6.www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/screening-tests-used.html.
7. Rex DK，Ahnen DJ，Baron JA，Batcs KP’Burke CA，BunRW，et al. Serrated lesions of the colorectum：Review and recommendations from an expert panel．Am J Gastroenterol. 2012 Sep;107(9):1315-29.
8. www.cancer.gov/types/colorectal/screening-fact-sheet.
9. Devesa SS．Chow WH．Variation in colorectal cancer incidence in the United States bv subsite of origin．Cancer. 1993 Jun 15;71(12):3819-26.
10. Jorge Perez. The Future of Colon Cancer Treatment. Archives in Cancer Research 2016, Vol.4 No.2:72.
11. M. Esteller. Non-coding RNAs in human disease. Nature Reviews Genetics, 2011, vol. 12, no. 12, pp. 861–874.
12. Armand-Labit V, Pradines A. Circulating cell-free microRNAs as clinical cancer biomarkers. Biomol Concepts. 2017 Apr 27. pii: /j/bmc.ahead-of-print/bmc-2017-0002
/bmc-2017-0002.xml.doi: 10.1515/bmc-2017-0002
13. Lizarbe MA, Calle-Espinosa J, Fernández-Lizarbe E, Fernández-Lizarbe S, Robles MÁ, Olmo N, Turnay J. Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs. Biomed Res Int. 2017;2017:7354260.
14. Ebert MS, Sharp PA. MicroRNA sponges: progress and possibilities. RNA. 2010 Nov;16(11):2043-50.
15. Ebert MS, Neilson JR, Sharp PA. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods. 2007 Sep;4(9):721-6.
