San – Cancer is always a problem that scientists are aiming to address as a result of their high levels of death in human. Because of that, many human bodyís ability was explored with the typical example of miRNA which is a new hope for cancer treatment. Previous studies have demonstrated the roles of miRNA in the diagnosis and treatment of cancer with regulation function in a lot of biological activities includes formation, development, differentiation or by detecting that the miRNA overactive causes cancer cells to live longer instead of apoptosis. This literature review will provide some background knowledge about miRNA, the effects of miRNA on gene that bringing the wonderful signal for cancer treatment and related researches. Cancer is always one of the top killers in the world and there are many causes for this disease. This is the reason why it attracts scientist to constantly explore the therapeutic approach.
It has resulted in many advanced treatments including chemotherapy, radiation therapy to fight cancer. However, because of the side effects that these treatment bring so much and can be dangerous to the human body, scientists continue to looking for more optimized and developed treatments. One of them is the discovery of miRNA that has made significant diagnosis and treatment of cancer. MicroRNA (miRNA) is a small RNA non-coding sequence, about 21-25 nucleotides in length. Each miRNA controls hundreds of gene expression through miRNA ñ mRNA binding. These non-transcriptional genes regulate many biological activities contains the formation, development, differentiation and even cell death. By estimation, miRNA-encoding genes account for 1-5% of the human genome and at least 30% of the total miRNA involved in gene regulation (MarFaclane et al, 2010).
The first miRNA was discovered in 1993 by Vitor Ambros et al is called lin-4 in Caenorhabditis elegans. MicroRNA synthesis involves cleavage processes that occur in the nucleus and then in the cytoplasm which are carried out by Drosha and Dicer enzymes in the RNase III group that are essentially endonuclease (MarFaclane et al, 2010). MicroRNA genes tend to be much longer than adult miRNA. Typical animal microRNA is made up of the following steps: -MicroRNA transcribes by RNA polymerase II form pri-miRNA. Pri-miRNA contains 5ícap and poly tail A. -Pri-miRNA is processed in the nucleus by a complex formed by RNase III Drosha enzyme and Pasha protein. Pre-miRNA was processed has a length of approximately 70 nucleotides. -Pre-miRNA is exported to the cytoplasm depend on the Exportin-5 and Ran-GTP complexes.
-In the cytoplasm, pre-miRNA continues to undergo Dicer RNase III enzyme process to produce complete miRNA with a length of 21-25 nucleotides. Although double miRNA sequences can work, only one sequence can active and form RISC (RNA-induced silencing complex) consisting of miRNA and their target mRNA interacting. The miRNA performs the function by the way that combine with the mRNA molecule follow the complementary rule and this leads to the silencing of the specific sequence in the mRNA molecule through one of the following processes: -Cutting the mRNA into two sections. -Making the mRNA unstable by cutting poly tail A. -Affecting the translation of mRNA into protein. MiRNA participate in the silent regulation process by attaching to the 3íUTR region of the mRNA, causing the mRNA to decay or the translation of mRNA molecule is blocked (Bartel, 2004).
Several recent studies have also shown that miRNAs are capable of binding to the 5í nontranslation region of the mRNA enhancing ribosomal protein translation (Orom et al, 2008). The pairing between central and mRNA base pair may completely or incompletely and determine the relative stability of miRNAs with mRNAs (MacFarlane et al, 2010). There are two mechanisms for explaining the dependence independence of the slicer molecule (Lujambio et al, 2012). For example, when there is complete mating between the central and mRNA sequence, it will spread out 10-11 nucleotides.
The products of the decomposition process are decomposed starting with mRNA molecule to remove poly tail A. Following the decomposition of mRNA is made by exosome. Silent regulatory that is not dependent on the slicer is incomplete mating between the miRNA and the mRNA target molecule leading to the inhibition of the cleavage activity of Ago2. Much empirical evidence suggests that in this way miRNA also promote the mRNA to deadenylation process, independent of the activity of the slicer, which inhibits the initiation of translation. Finally, mRNA molecules break down by exosomal pathways. Since the miRNA was discovered, it has been used as a biomarker for cancer treatment and is aimed at developing effective therapies for this chronic disease.
The publication of miRNA studies has focused on the use of miRNA as a potential biomarker for early cancer diagnosis. Reduced expression or loss of miRNA molecules acting as tumor suppressor genes leading to increased cell division results in tumor proliferation. For instant, in chronic lymphoblastic leukemia patients, most of the loss or diminution of two miRNAs was miR-15a and miR-16-1.
This reduction leads to the loss or degradation of the BCL12 gene (gene that suppresses cellular apoptosis and high in expression in tumor cells) (Calin et al, 2002). Some other miRNAs act as tumor suppressor genes such as miR-143, miR-145 shown in colorectal cancer, prostate cancer, miR-1, miR-101 and miR-122 shown in hepatocellular carcinoma (Sun et al, 2013). In addition, when miRNAs become active strongly, they can make cancer cells live longer, rather than into apoptosis. An experiment by Andrea Ventura has shown that miR-17-92 can be enhanced in some cancers, especially in the lung cancer and lymphoblastic B cancer. They found that the function of miR-17-92 is damaged in mouse embryos will cause death in mice due to their lung size is too small and all the B cell is death. This suggests that miR-17-92 plays a decisive role in the normal development of lung B cell.
In lymphocytes B, miRNA seems to play a role in promoting survival of the cell by blocking the genes of the apoptosis process. MicroRNA has played a huge role in cancer treatment and has not yet been fully explored. The most difficult is to create a way to get the miRNA to the right place for accurate cancer treatment. That motivates us to constantly create and emanate many achievements contributing to society.