More on microRNAs and why cancer spreads

This is another geeky post.  If you are currently having treatment for cancer the research described in this post will not alter your treatment as this work is being carried out in cells in a laboratory (and not in people) but it is very interesting and will hopefully be used to design new treatments in the future.

microRNAs are, as their name suggests, little bits of RNA (RNA is like DNA but different, read my earlier post on “microRNA’s and cancer – The science bit” if you want to know more).

We’ve only known about microRNAs for about a decade (we’ve known about DNA for about 50 years). So this research is cutting edge. A research group at MIT in America have discovered a microRNA that controls whether breast cancer spreads. They have published their results in the science journal “Cell”, you’ll need to pay to read the article called “A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis”

First things first, what does the title mean? Pleiotropic means something that can affect lots of other things, in this case mir-31 can alter the expression of 200 different genes. mir-31 is the name of one type of microRNA. The scientists show that miR-31 can stop breast cancer spreading.

Two of the scientists that did this reasearch are interviewed in a short (3 minute) video where they describe what they found and what this could mean.

If you can’t see the YouTube video try the Quicktime one on the Cell website  (in the supplemental information in the paper).

What are they actually saying?

Section 1 – Regulatory Roles of microRNAs

Scott (00 : 7 secs):

microRNAs are a highly conserved family of short regulatory RNAs…

This means that you find these RNAs in most plants and animals (so they are probably pretty important to life). These RNAs are found inside cells.

…appealing class of potential regulatory molecules…

These little RNAs can probably control (regulate) other things  in the cell. For example maybe the RNA could turn on or off some genes  (DNA is a type of molecule).

…in terms of their ability to modulate metastasis…

The scientists are looking at these little RNAs because they might be able to control whether a cancer spreads or not.  They use the word “modulate” to hedge their bets, maybe these RNAs will make cancer spread faster, maybe it will make it spread slower, no one knows  so we need to do the experiments.

…pleiotropically regulate a distinct number of mRNA targets…

This means that one little RNA can control several different things. He uses the word “distinct” which probably means they know exactly which things this particular RNA controls.

Robert (0:36 secs)

Scott’s boss starts off  by giving two examples that most biologists will be familiar with:

1. a kinase is a type of protein that can phosphorylate lots of other proteins and control them by turning them on or off.
2. a transcription factor is a protein that can bind to a gene and turn it on or off

He does this to “set the scene”, to show that in biology it is quite common for a single gene, protein or RNA to have an affect “pleiotropically” which means it will affect lots of different (but specific) things inside your cells. He then says it was Scotts job to try and find little RNAs that would stop cancer cells becoming aggressive (growing where they shouldn’t) and malignant (capable of spreading).

Section 2 – Identifying miR-31

Scott ( 1 min 05 secs):

….involved a screen, based on an expression panel of 15 different breast cell lines that we have in the lab…

To find the miR-31 RNA they looked at 15 different types of breast cancer cells that they were able to grow in the lab. Some of these breast cancer cells were “nastier” than others, they could form tumours and spread faster. They measured how much miR-31 was in each different type of breast cancer and then looked to see how quickly these tumours spread.

Robert (1 min 35 secs):

If you want to know the details, read the paper, but the interesting point is that Scott has discovered a microRNA that works really well at stopping the aggressive behaviour of tumours.

…also controls the normalcy of the epithelial cells residing in normal cell layers in normal tissue…

This statement is a rather complicated way of saying that while this little RNA is important in cancer, it might also be important in everybody, in normal cells. Epithelial cells are cells that line your body, everybody has them (and you need them to survive).  Most types of breast cancer develop from epithelial cells.

Section 3 – miR-31 impeded metastasis.

Scott (2 mins 07 secs):

…is it’s ability to act, apparently on several different steps of the so called invasion metastasis cascade…

The little RNA (miR-31) does more than one thing to stop cancer cells from moving and spreading.

…a series of sequential events by which a tumour is able to grow out into a macroscopic secondary tumour…

This sentence is supposed to help you understand what he means by the “invasion metastasis” cascade. Basically it means the step by step process that happens when a bit breaks of from a primary tumour and forms a secondary tumour somewhere else in the body (e.g. a breast cancer can spread to the lungs or bone or brain).

Robert (2 mins 50 secs):

…this particular microRNA [miR-31] acts as a very strong impediment to the development of highly aggressive diseases…

The little RNA stops “nasty” tumours from spreading. So maybe tumour develop ways to stop this RNA working and that is why they can grow and spread when they shouldn’t.  He finishes by saying that although they have only done the experiments in breast cancer cells, it could, potentially, apply to lots of other aggressive types of cancer.

So to sum up, these scientists found that if a tumour did NOT spread then it had lots of miR-31 RNA.  If a tumour DID spread then it had low levels of miR-31 RNA. Perhaps, in the future we will be able to measure the amount of miR-31 in people and tell if their cancer is going to spread (or not). That means if someone has high amounts of miR-31 then they might not need as much chemo or radiotherapy as someone with low amounts of miR-31.  This is all speculation as no experiments have been carried out in people, yet.

If you want to learn more about this there are articles in Science News Daily and NanoTechWire.com.

Do scientists speak a foreign language? Did you find tye video interesting or was it all just gobbledegook?

Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szász AM, Wang ZC, Brock JE, Richardson AL, & Weinberg RA (2009). A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell, 137 (6), 1032-46 PMID: 19524507