Regulation of cancer stemness, cell signaling, reactive oxygen species, and microRNAs in cancer stem cells

MicroRNAs (miRNAs/miRs) are a class of endogenous short or small noncoding RNAs (sncRNAs) that play an intrinsic role in the regulation of various cellular, physiological, and developmental processes. Aberrant expression of miRNAs is often associated with numerous diseases including various cancers. Recent evidences support that miRNAs are involved in enriching cancer stem cell (CSC) population. CSCs are small subpopulation of cells that have the potential to initiate tumor formation and are involved in the tumor progression, metastasis, relapse, and cancer drug resistance. They have unique features such as self-renewability, multilineage-differentiation potential, proliferation of differentiated progeny, and expression of specific cell surface stemness or stem cell markers. miRNAs are shown to enhance the stemness properties of cancer cells and also CSCs that drive tumorigenesis. miRNAs are involved in regulating the expression of crucial stemness molecules, stem cell transcription factors, and reactive oxygen species (ROS) in cancer cells and CSCs, and thus promote cancer stemness. They also aberrantly activate various critical cancer cell and stem cell signaling pathways that directly trigger the cancer cells and CSCs during tumor development and progression. The levels of various miRNAs and their regulations in cancer cells and CSCs are linked to poor prognosis of cancer in patients. In this chapter, we discussed on the molecular interactions and regulation of cancer stemness markers, key cell signaling pathways, miRNAs, and ROS in CSCs and cancer cells, and their dysregulations that contribute to cancer progression, metastasis, therapeutic resistance, and cancer relapse.