RNA Molecules and Cancer Cells

Even before taking AP Bio, I have always been fascinated by diseases, particularly how cancer works. Several years ago, my aunt was diagnosed with it (she has recovered since) but it got me thinking about how this disease works and why a cure hasn't been found yet. There are treatments, chemotherapy, for example, is usually a patient's first option for treatment. Chemotherapy essentially kills millions of cells in the patient's body. The drug targets cells that exhibit cancer cell-like behavior and kills them off. However, healthy cells may exhibit these behaviors too, causing harmful side effects to the patient. Chemotherapy can kill off healthy cells that also divide quickly similar to cancer cells, such as those that allow hair growth or the ones in our intestine (causing hair loss, vomiting, among other side effects). As a result of this, chemotherapy puts an incredible strain on the patient's body. 

image credit: https://www.verywellhealth.com/cancer-cells-vs-normal-cells-2248794 

Scientists have been working for years to come up with alternatives to chemotherapy, and while a new treatment hasn't been made just yet, a new method of approaching one has been. I found it super fascinating when I read that microRNA and mRNA, which are involved in protein regulation, are found to make excellent targets for drugs and medicines. MicroRNAs regulate mRNAs, which code for the proteins that make up our bodies and thus, can prevent protein synthesis.

Researchers are studying a type of microRNA known as miR-34a, which can help regulate the activity of p53, a protein that regulates the cell cycle. Mutations in this protein can cause cancer since cells will uncontrollably divide. What miR-34a does is it reduces the amount the mRNA present that code for Sirt1, which is a protein that deactivates p53 and can cause cancer. Below is a diagram showing how this process works.

But how do they know this method could work? You can't really just guess at these things. Researchers have recently analyzed the structure and dynamics of miR-34a when it binds to mRNA and found a structural complex that can exist in two states. One is super active and the other isn't as active. These states can interconvert, and the frequency of each of the states can be changed by external factors (such as different drugs or treatments) which is super cool in my opinion. External factors controlling the different states can be used to control protein production (of not just Sirt1) and in the end, help fight off cancer.

As for current research and trials to test this new method, I couldn't really find any trials going on right now so I would assume they are planning to conduct some more thorough research soon. 

I did find a paper/article about the role of miR-34a in cancer, a lot of it was rather confusing to me but I think it's quite informative so here's the link to that

I find it amazing that researchers are discovering more and more about the mechanisms behind how cancer occurs in people. The research being done on the disease is remarkable in my opinion and I hope that eventually a less harmful treatment is made, or even a cure someday. When I go off to college, I hope to study molecular/cellular biology and hopefully learn more about how diseases such as cancer work as well. Diseases/viruses have always intrigued me so I hope to do research in that area of study when I am older. 

Oh and one last thing, I love making science and math memes since humor just makes everything fun, so researching this topic made me want to make some memes about this. I made two right here:

Zombie Deer Disease and Why We Should Fear it

This is the Zombie Apocalypse we should really be fearing because it is right at our doorstep. Now of course "Zombie Deer Disease" does not actually bring any deer back from the dead, they may just look like extras from The Walking Dead - Deer Edition. 

The proper name for this disease is Chronic Wasting Disease (CWD) and it is a progressive fatal degenerative neurological disease. Yeah, I know that all those words together are pretty freaking scary, however, you are in luck because so far it has only affected cervid populations. Cervids are the deer family, so moose, elk, mule deer, whitetail deer, reindeer, etc. and are found in all continents except Australia and Antarctica. CWD has been found in cervid populations in Canada, the United States, Norway, and South Korea (through imported deer). CWD is also a Transmissible Spongiform Encephalopathy or TSE, other TSEs are Bovine Spongiform Encephalopathy or Mad Cow disease, Scrapie, Creutzfeldt-Jakob Disease, and Fatal Familial Insomnia. TSEs are caused by abnormal proteins called prions.

A Healthy Stag (https://en.wikipedia.org/wiki/Deer#/media/File:Family_Cervidae_five_species.jpg)

Effects:
The effects of CWD are pretty scary they include holes eaten into the brain, drastic weight loss, lack of coordination and lack of fear of people (https://www.cdc.gov/prions/cwd/cwd-animals.html). Other than the obvious eating holes in the brain of the deer part there are also other reasons that this can wreak havoc on the populations. Discoordinated deer cannot protect themselves against predators like other deer can and they also do not realize that they should see humans as a threat. Also, deer with CWD by some reports die at a rate 3 times that of unaffected deer yearly. There are a few major problems that are hindering efforts to prevent CWD, first it has a really long incubation period of somewhere between 18 to 24 months and physiological symptoms do not show up until the very end. Also, it is really contagious among cervid populations and no one knows how to stop it yet. The main reason for the lack of prevention is it is not known how it is transmitted and even by depopulating any area it doesn't stop it from coming back in a totally new population later put in the area. Another reason that there is a problem is that not much can be done with the populations because no one knows how to stop it.

Deer suffering from CWD (https://www.nih.gov/news-events/news-releases/nih-study-finds-no-chronic-wasting-disease-transmissibility-macaques)

Research:

Luckily research has started to do with a few different aspects of CWD. At the University of Minnesota, they got $1.5 M to fund research into improving testing for CWD (https://www.vetmed.umn.edu/departments/veterinary-and-biomedical-sciences/spotlight/drs-pam-skinner-and-peter-larsen-aim-18m-funding-speed-chronic-wasting-disease-testing). Research was also done by the University of Wyoming to test the effects of CWD on cattle and it was found that cattle resist exposure to CWD which is good because it means that right now at least it will probably not transfer to cattle populations (http://www.uwyo.edu/uw/news/2018/05/long-term-research-shows-domestic-cattle-resist-oral-exposure-to-chronic-wasting-disease.html). The NIH also did a study to see if there was transmissibility of CWD to the primate Cynomolgus Macaque or Crab-eating Macaque for which they found no transmissibility which for humans is a good sign (https://jvi.asm.org/content/92/14/e00550-18).

Cynomolgus Macaque (https://www.nc3rs.org.uk/macaques/macaques/behaviour-and-communication/)

The Spread:
The best piece of news for humanity is actually that there is no piece of evidence for human risk yet. It has even been determined by some that most of the time a human can even eat deer meat infected with CWD. However, the threat of CWD is becoming more prevalently all the time with it now being in 21 states in the US.

Distribution of CWD in North America (https://www.usgs.gov/media/images/distribution-chronic-wasting-disease-north-america-0)

If you are interested, more information about CWD can be found at the CDC page of CWD (https://www.cdc.gov/prions/cwd/index.html) and at the CWD website (http://cwd-info.org/faq/).