Team:NJU-China/Results/Conclusions
Conclusions
Overview of cancer
Undeniably, no matter what we pursue, it is the health and wellness that people care about most. Everyone goes for a healthier and stronger body, but we are all clear about that there are numerous diseases around us, and it's still clueless for us to completely resist and cure a large quantity of them. People usually feel uncomfortable and scared by intractable and severe diseases. And cancer must be one of the nightmares.
Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. Once the spread, also known as metastasis, isn’t well controlled, it can result in death[1] . As one of the most frightening death threat, cancer can be aggressive and malignant. The harmful effects of cancer on individual, family and society are enormous and appalling.
Global
According to WHO and the latest global cancer statistics (2015), there were 14.1 million new cancer cases in 2012 worldwide and the corresponding estimates for total cancer deaths were 8.2 million (Fig. 1). Literally, about 22,000 cancer deaths happened a day. Besides, 1 in 7 deaths was related to cancer, and cancer caused more deaths than AIDS, tuberculosis and malaria combined. By 2030, the global burden is expected to grow to 21.7 million new cancer cases and 13 million cancer deaths on account of rapid growth and aging of population[1] . Due to the adoption of lifestyles that are known to increase cancer risk, such as smoking, poor diet, physical inactivity and reproductive changes (including lower parity and later age at first birth) in developing country, it’s reasonable to estimate that the actual figures will be considerably larger[2] .
Therefore, cancer is becoming one of the leading causes of death and the major public health problem around the world (Fig. 2).
Design
RNAi & KRAS
RNA interference (RNAi) is an emerging technology of gene silencing. It uses siRNA segments to destroy specific mRNA, thereby, shut down the expression of target genes. RNAi has been demonstrated as a novel treatment modality of cancer and we decided to utilize this technology to silence the expression of specific oncogene[1]. KRAS is one of the most commonly mutated oncogenes in lung cancer. The mutation rate of KRAS can be up to 25% in NSCLC (a main type of lung cancer)[2]. Thus, we picked KRAS as our target oncogene. Then we designed anti-KRAS siRNA as a therapeutic agent to degrade KRAS mRNA, therefore, repressing the expression and function of K-ras protein. We used a specialized software developed by team SYSU-software to find the ideal siRNA sequence. This tool also designed pairs of oligonucleotides needed to generate short hairpin RNAs (shRNAs) in the plasmid. When the shRNA plasmids of KRAS are transfected into HEK293 cells, the dsRNA is cleaved into siRNA of KRAS by the enzyme Dicer, and then target KRAS mRNA. However, due to the short half-life period and poor cellular uptake of exogenous siRNA[3], an efficient delivery vehicle is needed to stabilize and enhance the naked small interference molecule's function.
DEMONSTRATE
