Abstract
Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden. However, most anti-cancer treatments face the problems of tumor recurrence and metastasis. Therefore, finding an effective cure for cancer needs to be solved urgently. Recently, the discovery of cancer stem cells (CSCs) provides a new orientation for cancer research and therapy. CSCs share main characteristics with stem cells and are able to generate an entire tumor. Besides, CSCs usually escape from current anti-cancer therapies, which is partly responsible for tumor recurrence and poor prognosis. microRNAs (miRNAs) belong to small noncoding RNA and regulate gene post-transcriptional expression. The dysregulation of miRNAs leads to plenty of diseases, including cancer. The aberrant miRNA expression in CSCs enhances stemness maintenance. In this review, we summarize the role of miRNAs on CSCs in the eight most common cancers, hoping to bridge the research of miRNAs and CSCs with clinical applications. We found that miRNAs can act as tumor promoter or suppressor. The dysregulation of miRNAs enhances cell stemness and contributes to tumor metastasis and therapeutic resistance via the formation of feedback loops and constitutive activation of carcinogenic signaling pathways. More importantly, some miRNAs may be potential targets for diagnosis, prognosis, and cancer treatments.
Highlights
Cancer is a neoplasm characterized by uncontrolled cell growth and the ability of invasion
Krüppel-like factor 4 (KLF4)/phosphatidylinositol 3-kinase (PI3K)/Akt/p21 pathway, miR-7 attenuates cancer stemness, which is sustained for generations, and miR-7 could be a potential marker for Prostate cancer (PCa) prognosis and treatment [105]
tumor necrosis factor receptor-associated factor4 (TRAF4) interacts with p75NTR and inhibits subsequent NF-κB pathway activation [156]. miR-21-3p suppresses TRAF4 expression, and p75NTR is present in cancer stem cells (CSCs) and activates the NF-κB pathway, restraining cell apoptosis as well as maintaining CSC phenotypes [157]
Summary
Cancer is a neoplasm characterized by uncontrolled cell growth and the ability of invasion. During the late 1990s, studies have shown in acute myeloid leukemia cell transplantation that only cells expressing CD34+ CD38− form the entire tumor, which are the CSCs of leukemia [7]. Besides the stem cell-like properties of proliferation and self-renewal, CSCs have other crucial characteristics as well (Figure 1). Due to the ongoing studies and acknowledgement of CSCs’ properties, the significance of developing CSC-targeted cancer therapies in the case of recurrence and metastasis cannot be underestimated. Plenty of studies have proven that overexpression or downregulation of various miRNAs in cancers might regulate CSC proliferation and metastasis to facilitate cancer development. We mainly focus on the relationship between miRNAs and CSCs in the eight most common cancers, hoping to cast new light on miRNA-targeting therapy
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