miRNAs modulate cancer stem cells

Cancer stem cells are a group of cells within cancer which were imagined some 150 years ago, to be responsible for the development of cancer. These cells were not analyzed further at that time because of the absence of necessary means and instrumentation. However later with more and more studies, developments and instrumentation, these cells were de-novo discovered in acute myeloid leukemia. During the period of last 2 decades these group of cells, with specific characteristics have been discovered in large number of solid tumors. These cells are commonly characterized by self renewal, differentiation, growth promotion, chemotherapeutic and radio-resistance, invasion and metastasis. They may remain dormant and survive for long times; and get activated when excited by correct signal or impulse. These cancer stem cells are organ specific and have special niche like bone marrow for hematopoietic cells. These can be grown in culture and can be transplanted at other site/ organ.

What regulates these cancer stem cells' special properties, has not been absolutely clear, but for a large part it has come to be worked-out that these are governed by miRNAs besides other factors.

miRNAs are a group of small; non-coding RNAs, usually 21-23 nt long. These were previously thought to be inert and non-functional. Later studies revealed their action during transcription and regulation on cell activities. These are achieved by affecting the proteins and molecules that regulate signal transduction pathways.

These microRNAs can either upregulate or down regulate tumor suppressor genes or vice-versa. These are tissue specific or stage specific miRNAs, cause metastasis by either promoting metastasis related genes; otherwise they can also suppress metastasis related genes which will result in either no metastasis. These miRNAs also act as part of communicating system between cell to cell; and affect signaling pathways. The important signaling pathways involved in cancer development are Wnt/B-Catenin, Notch and Hedgehog signaling pathways. These regulate cancer stem cells' self renewal, tumorigenesis and differentiation.

miRNAs have also been envisaged as very promising entities in treatment of cancer as well. This is possible because if a miRNA could be delivered within a cancer cell of the tumor it can upregulate oncogenic processes or down regulate them. If the miRNA used is of down regulating type, it shall kill the cancer cell but not harm the normal cells. However the secure delivery of miRNA within the cell remains a big problem. It is because endonucleases within the cell would degrade miRNA.

However, scientists are trying different ways of delivering it within the cell through different means and one is of them through nano particles, nano-capsules etc. Acid-lipid combination molecules are not acted upon by endonucleases. The practicality of these approaches is a matter of time but the hypothesis stands good chances success.

Breast cancer stem cells were not only one of the first to be detected, isolated and studied in great detail, but also offered many clear concepts. Here only, it was recognized that not one factor like let - 7, but many miRNAs played important roles and one such was miRNA-30, which was markedly reduced in breast cancer stem cells. Thus, utilizing the action of both let-7 and miRNA-30, it was possible to achieve better control of tumorigenesis. However till more factors and miRNAs continue to be discovered with time.