Oncomir

Key takeaways

Oncomir belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Oncomir to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Oncomir from memory before moving on to harder problems.

Reference excerpt

An oncomir (also oncomiR) is a microRNA (miRNA) that is associated with cancer. MicroRNAs are short RNA molecules about 22 nucleotides in length. Essentially, miRNAs specifically target certain messenger RNAs (mRNAs) to prevent them from coding for a specific protein. The dysregulation of certain microRNAs (oncomirs) has been associated with specific cancer forming (oncogenic) events. Many different oncomirs have been identified in numerous types of human cancers. Oncomirs are associated with carcinogenesis, malignant transformation, and metastasis. Some oncomir genes are oncogenes, in that overexpression of the gene leads to cancerous growth. Other oncomir genes are tumor suppressors in a normal cell, so that underexpression of the gene leads to cancerous growth.

General mechanism Oncomirs cause cancer by down-regulating genes by both translational repression and mRNA destabilization mechanisms. These down-regulated genes may code for proteins that regulate the cell's life cycle. Oncomirs may be at increased or decreased levels within cancerous tissue. In the case of increased oncomir activity, the oncomir is likely suppressing a tumor suppressor gene. In cases of underexpressed oncomirs, regulation is attenuated, allowing the cell to proliferate freely. Viruses have also been found to have miRNA that mimic parts of natural regulatory human miRNA's. One example is the Epstein–Barr virus (EBV) which is associated with various types of cancer.

History The first link between miRNA and the growth of cancer was reported in 2002 when researchers observed a down-regulation of miR-15a and miR-16-1 in B-cell chronic lymphocytic leukemia patients. The term is a portmanteau, derived from "oncogenic" + "miRNA", coined by Scott M. Hammond in a 2006 paper characterizing OncomiR-1.

Oncomir addiction Certain tumors may be "addicted" to oncomirs, meaning that in order to remain tumors, a constant concentration of oncomirs must be present. This is demonstrated by inactivation of the oncomir miR-21. Mice expressing miR-21 contracted pre-B malignant lymphoid-like phenotype tumors. After inactivation of miR-21, the tumors completely regressed. This addiction is part of a more general phenomenon involving oncogenes, called oncogene addiction.

Potential clinical uses of miRNA Studies have been performed to evaluate the effectiveness of miRNAs as potential markers for cancers. MicroRNAs have shown promise in this area due to their stability and specificity to cells and tumors. A recent study investigated the use of miRNA as a biomarker in pancreatic ductal adenocarcinoma, a form of pancreatic cancer. The study analyzed RNA from biopsied pancreatic cysts to identify deviations in expression of miRNAs. The study found that 228 miRNAs were expressed differently relative to normal pancreatic cells. Included in the findings was an association between hepatocellular carcinoma and the upregulation of miR-92a, a member of OncomiR-1. Extracellular microRNAs (exRNAs) may also be useful in clinical cancer detection. For example, in a study of cancer patients with a type of lymphoma called diffuse large B-cell lymphoma (DLBCL), serum levels of three miRNA's, miR-21, miR-155 and miR-210, were higher in cancer patients than in healthy controls. In particular, patients with high expression of miR-21 were more apt to have a relapse-free survival. (A table listing cancer type and the associated exRNA biomarker candidates can be found in Kosaka et al..)

Identified oncomirs

The OncomiR-1 line The OncomiR-1 cluster of miRNA's is one of the best characterized set of mammalian miRNA oncogenes. The oncomir-1 gene, also known as mir-17-92, encodes a single mRNA transcript that folds into six stem loops. Several cancer-associated oncomirs are generated from these stem loops, including miR-17, miR-18, miR-19a, miR-20, miR-19b, and miR-92. It has been shown that miRNA's from the OncomiR-1 line inhibit cell death, thus increased expression of oncomir-1 leads to the development of tumors. The oncomir-1 products inhibit expression of the transcription factor E2F1, which may impact apoptosis via the ARF-p53 pathway. It is predicted that there are several hundred target mRNAs for each miRNA, and therefore likely many additional targets for the OncomiR-1 line

OncomiR Resources and Databases There are a few online resources and databases for collecting and annotating the oncogenic and tumor-suppressive miRNAs: OncoMir Cancer Database Online database to access TCGA miRNA sequencing based expression data from over 10,000 tumor and normal tissues. OncomiRDB Archived 2018-03-01 at the Wayback Machine: a database for the experimentally verified oncogenic and tumor-suppressive microRNAs. miRCancer: microRNA Cancer Association Database HMDD Archived 2014-05-06 at the Wayback Machine: Human microRNA Disease Database PhenomiR Archived 2014-05-06 at the Wayback Machine: a knowledgebase for microRNA expression in diseases and biological processes Oncomir A collection of microRNA expression databases

Characteristics and mechanisms of some well defined oncomirs

miR-17

MicroRNA-17, or miR-17, is a member of the OncomiR-1 family and one of the first miRNA to be identified as an oncogene. miR-17 has been confirmed to target the cell cycle transcription factor E2F1, a protein that not only promotes cell growth but also death.

miR-19

MicroRNA-19, or miR-19, is a member of the OncomiR-1 family, and consists of three sub classifications in both humans and mice: mir-19a, mir-19b1 and miR-19b2. miR-19 has been shown to downregulate phosphatase and tensin homolog (PTEN) effectively increasing activity of the cellular survival-promoting signal pathway PI3K-Akt.

miR-21

MicroRNA-21, or miR-21, a specific oncomir, becomes more abundant in human cancer. MicroRNA-21 elevation has been found in a wide variety of cancers, including glioblastoma, breast, colorectal, lung, pancreas, skin, liver, gastric, cervical, thyroid, and various lymphatic and hematopoietic cancers. It has been found to down-regulate the tumor suppressor PDCD4, thus aiding in the cancer's invasion, intravasation and metastasis.

miR-155

MicroRNA-155, or miR-155, is a commonly over-expressed oncomir in human cancers. In human breast cancer, it has been identified to target the gene which encodes for a protein called suppressor of cytokine signaling 1 (SOCS1). Recent research suggests that miR-155 negatively regulates SOCS1, but may be a feasible target in breast cancer therapy.

miR-569

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Oncomir

Start with the simplest possible case. Write down what Oncomir claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Oncomir before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Oncomir ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Oncomir

In research: Oncomir appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Oncomir in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Oncomir is common in secondary-school and first-year university syllabi. It links to neighbouring topics Carcinogenesis, RNA, so understanding it makes those chapters shorter.
In everyday life: Look for Oncomir outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Oncomir in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Oncomir means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Oncomir out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Oncomir in simple terms?

An oncomir (also oncomiR) is a microRNA (miRNA) that is associated with cancer. MicroRNAs are short RNA molecules about 22 nucleotides in length.

Why does Oncomir matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Oncomir?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Oncomir.