Mignonette H. Macabali
Introduction Brief Review of “The Central Dogma” Cancer genes Genetic Changes in Colorectal Cancer
The Central Dogma                                                                                        Types of Proteino...
Cancer                                                        Oncogenes (ex., src –                                      ...
Genetic Changes inColorectal Cancer
TOPIC PROPER
 or “miRNAs” are small regulatory RNAs ≈22 to 26 nt in length First seen: C. elegans (Lee et al., 1993; Wightman et al...
The central dogma of molecular biology suggests  that the primary role of RNA is to convert the  information stored in DNA...
Types of ProteinmiRNA function
miRNA detection methods (1)Northern blotting  RNANice to know: • Southern blotting    DNA, 1st blottingtechnique by Edwin...
miRNA detection methods (2)Quantitative Reverse Transcription – Polymerase Chain Reaction (qRT-PCR)Real Time - PCR
miRNA detection methods (3)Micro Array technique
miRNA expression profiles
Studies on miRNA functionin Colorectal Cancer   Asangani IA, Rasheed SA, Nikolova DA, et al. MicroRNA-21 (miR-21) post-tr...
Other research areas formiRNA in Colorectal Cancer Fecal miRNA detection Therapeutics
Future Directions issues still need to be resolved: (1) the standard method for miRNA   quantification,(2) effective and ...
End of Presentation
Micro rna edsc350_macabali
Micro rna edsc350_macabali
Micro rna edsc350_macabali
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  • Involves three major players: DNA, RNA, and Protein. It also involves 3 processes, namely: Replication, Transcription and Translation or protein synthesis. These major chemical components and processes form the basis of storage, transmission and expression of hereditary information.
  • An oncogene is a gene that, when mutated or expressed at high levels, helps turn a normal cell into a tumor cell.Many abnormal cells normally undergo a programmed form of death (apoptosis). Activated oncogenes can cause those cells to survive and proliferate instead. Most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection, to cause cancer. Since the 1970s, dozens of oncogenes have been identified in human cancer. Many cancer drugs target those DNA sequences and their products. Tumor suppressor genes - are genes that regulate the growth of cells. When these genes are functioning properly, they can prevent and inhibit the growth of tumors.When tumor suppressor genes are altered or inactivated (due to a mutation), they lose the ability to make a protein that controls cell growth. Cells can then grow uncontrolled and develop into a cancer. There are 3 main types of tumor suppressor genes. One type tells cells to slow down and stop dividing. Another type is responsible for fixing damages in DNA that can happen when cells divide. A third type is responsible for telling cells when to die, a process called apoptosis.
  • As long as suppressor genes function normally, all goes well. If, however, suppressor genes are damaged or lost, they are no longer available to maintain order. As a result, a cell may begin to divide in an unusual way. If more and more suppressor genes don't work, the division process may become more and more unruly, resulting in the loss of more and more genes. In time, a cancer cell may be formed. This process is shown in Figure 2 below for the formation of a non-hereditary colon cancer cell. As you can see, it's like the straw that breaks the camel's back: once enough suppressor genes are not working, the cell can become a cancer cell. The changes shown in Figure 2 are known to occur in the formation of a non-hereditary colon cancer cell. All of the genetic changes needed to produce a cancer take place after conception in a single cell and its descendents, so it takes time for all of the changes to accumulate in one cell. That's probably why most non-hereditary cancers are diagnosed at older ages, not younger ages.
  • The northern blot is a technique used in molecular biology research to study gene expression by detection of RNA (or isolated mRNA) in a sample.[1][2]Flow diagram outlining the general procedure for RNA detection by northern blotting.With northern blotting it is possible to observe cellular control over structure and function by determining the particular gene expression levels during differentiation, morphogenesis, as well as abnormal or diseased conditions.[3] Northern blotting involves the use of electrophoresis to separate RNA samples by size and detection with a hybridization probe complementary to part of or the entire target sequence. The term 'northern blot' actually refers specifically to the capillary transfer of RNA from the electrophoresis gel to the blotting membrane. However, the entire process is commonly referred to as northern blotting.[4] The northern blot technique was developed in 1977 by James Alwine, David Kemp, and George Stark at Stanford University.[5] Northern blotting takes its name from its similarity to the first blotting technique, the Southern blot, named for biologist Edwin Southern.[1] The major difference is that RNA, rather than DNA, is analyzed in the northern blot.[6]
  • Micro rna edsc350_macabali

    1. 1. Mignonette H. Macabali
    2. 2. Introduction Brief Review of “The Central Dogma” Cancer genes Genetic Changes in Colorectal Cancer
    3. 3. The Central Dogma Types of Proteinof MolecularGeneticsor simply “Central Dogma”Module 4, p.44 EDSC 350http://www.nvo.com/jin/scrapbookcell/view.nhtml?profile=scrapbookcell&UID=10023 Types of protein images from book Essential Cell Biology by Alberts, (2004)
    4. 4. Cancer  Oncogenes (ex., src – sarcoma)  Proto-oncogene  Activated oncogene  Tumor-suppressor gene (types, fcn.:) (ex p53 gene)  Cells stop dividing  Fix DNA damages  induce apoptosisGenetic changes cause normal cells to become cancerous. Credit: NCI, NIH
    5. 5. Genetic Changes inColorectal Cancer
    6. 6. TOPIC PROPER
    7. 7.  or “miRNAs” are small regulatory RNAs ≈22 to 26 nt in length First seen: C. elegans (Lee et al., 1993; Wightman et al., 1993) Also found in many other species, including flies, mice, plants, and humans
    8. 8. The central dogma of molecular biology suggests that the primary role of RNA is to convert the information stored in DNA into proteins. http://www.nvo.com/jin/scrapbookcell/view.nhtml?profile=scrapbookcell&UID=10023 In reality, there is much more to the RNA story. Clancy, S. (2008) RNA functions. Nature Education 1(1)
    9. 9. Types of ProteinmiRNA function
    10. 10. miRNA detection methods (1)Northern blotting RNANice to know: • Southern blotting DNA, 1st blottingtechnique by Edwin Southern•Western Blotting •Protein•Eastern Blotting •Post-translational modifications of proteins
    11. 11. miRNA detection methods (2)Quantitative Reverse Transcription – Polymerase Chain Reaction (qRT-PCR)Real Time - PCR
    12. 12. miRNA detection methods (3)Micro Array technique
    13. 13. miRNA expression profiles
    14. 14. Studies on miRNA functionin Colorectal Cancer Asangani IA, Rasheed SA, Nikolova DA, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 2008;27(15):2128–36. Bandres E, Cubedo E, Agirre X, et al. Identification by real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer 2006;5:29. Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J, Kerin MJ. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg 2010;251(3):499–505. Brase JC, Wuttig D, Kuner R and Sultmann H (2010). Serum microRNAs as non-invasive biomarkers for cancer Molecular Cancer 2010, 9:306 Chang KH, Mestdagh P, Vandesompele J, Kerin MJ, Miller N. Micro-RNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer. BMC Cancer 2010;10:173. Schetter AJ, Leung SY, Sohn JJ, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocar- cinoma. JAMA 2008;299(4):425–36.
    15. 15. Other research areas formiRNA in Colorectal Cancer Fecal miRNA detection Therapeutics
    16. 16. Future Directions issues still need to be resolved: (1) the standard method for miRNA quantification,(2) effective and tissue-specific delivery method, and(3) cost-effective miRNA synthesis technique. More detailed pre-clinical and clinical studies comparing miRNA-based diagnostics, treatments, and therapeutics with current, equivalent modalities
    17. 17. End of Presentation

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