A ray of hope for treatment-resistant cancers: Using Micro-RNA

MicroRNAs (miRNAs) are biological molecules responsible for controlling protein synthesis at the genetic level. A newly discovered miRNA class appears effective in preventing cancer cell proliferation.

We discussed miRNAs and their functions in our article Can cancer-causing genes be silenced? . To prevent a protein from being produced, miRNA binds to its mRNA during the mRNA stage of protein synthesis. The resulting complex is double-stranded. Our immune system recognizes freely circulating double-stranded DNA as viral DNA, attacks and eliminates it.

Targeting the cause of cancer development!

Studies of microRNA use in cancer treatment have increased recently, mainly because microRNAs target “the cause of cancer development.” New research showed miRNAs could be used for treatment-resistant cancers. Genetic analyses aimed to identify miRNAs directly regulating cyclin/CDK protein activity, which controls human cell proliferation. They discovered miRNAs able to target most cyclin/CDKs. When tested in mouse models, these miRNAs prevented tumor progression.

Scientists do not give up…

Cyclin/CDKs play important roles in the cell cycle. Many tumors show excessive activity of these molecules. However, they are diverse, and when one is inhibited, another can replace it. Blocking a single cyclin/CDK type is therefore insufficient to stop tumor cell growth. Discovery of a miRNA class able to target almost all cyclin/CDKs makes this research important.

What does this study mean for cancer treatment?

• Cancer develops when accumulated gene damage (mutations) produces faulty or nonfunctional proteins, disrupting normal cell structure. Most damage occurs in genes producing proteins that control cell proliferation. Gene damage leads to excessive production or altered functions of proteins. Targeting these genes with microRNAs could be an important cancer treatment strategy because it targets cancer’s cause.
• The study is important for discovering microRNAs that regulate the activity of genes controlling cell proliferation.
• A difficulty in treating cancer with microRNAs is delivering them effectively to the tumor. Blood circulation contains many enzymes that break down nucleic acids (DNA or RNA), so microRNAs are easily degraded. Recently, nanotechnology has been used in efforts to develop microRNA carrier systems.
• It must be emphasized that laboratory research on microRNA cancer treatments continues.

Further reading for science enthusiasts: What is the cell cycle? How is cell proliferation controlled? What do cyclin/CDKs do?

Our cells’ “life cycle” consists of G1, S, G2 and M phases. Cells begin dividing when they reach a certain size. G1 is preparation. During S, DNA is replicated so equal genetic information passes to daughter cells. In G2, the cell prepares for mitosis. Two identical cells result after mitotic division.

Cell proliferation in our body is controlled by a sensitive system consisting primarily of 3 checkpoints. The figure below shows how the proliferation mechanism is controlled.

• The first checkpoint is G1/S’. It checks whether the cell has sufficient energy to multiply, its size and the presence of growth factors. If conditions are suitable, cyclin/CDK proteins activate, allowing passage. A cell unable to pass G1 remains in G0, the “resting/dormant” phase.
• The second checkpoint is G2/M’. It checks the quality of replicated DNA. If DNA is damaged , the cell cannot pass this checkpoint.

- Related topic: The work that earned Aziz Sancar the Nobel Prize: Mechanistic repair of DNA

• The third checkpoint concerns spindle fibers. As cells divide, they must pass equal DNA to daughter cells. Spindle fibers separate chromosomes equally. If separation is improper, one daughter cell receives a different number of chromosomes, leading to genetic diseases. This checkpoint checks whether fibers separate chromosomes correctly. A cell passing it proceeds to mitosis and begins dividing.