Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden

Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden. 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 Ned 19 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. and gene promoter, named TFBS A and B. Studies have shown that it is only when SOX2 binds to TFBS B alone that it can inhibit miR-200c transcription. Normally, SOX2 binds to TFBS A rather than TFBS B. In addition, miR-200c also suppresses the activation of the PI3K/Akt pathway in CSCs, but the inhibitory effect of miR-200c on the PI3K/Akt pathway can be restored by SOX2. The miR-200c/SOX2 feedback loop finally elevates SOX2 expression and promotes CSCs characteristics; it should be regarded as a positive feedback loop. However, the reason why the authors recognized it as a negative loop might be that considering miR-200c, it is suppressed by its downstream target. In conclusion, the novel miR-200c/SOX2 negative feedback regulatory loop could be a promising therapeutic target for CRC treatment [83]. 4.5. miR-30-5p In the CRC cell lines Caco2, HT29, HCT15, HCT116, SW620, and SW480, miR-30-5p suppresses stem marker expression and tumorsphere formation, inhibits CSC proliferation, and decreases resistance by inhibiting the expression of ubiquitin-specific peptidase 22 (USP22). USP22 is involved in regulating some oncogenic pathway activation [84]. In Ned 19 CRC, Ned 19 because of the low expression of miR-30-5p, USP22 activates the Wnt/-catenin pathway by increasing the nuclear concentration of -catenin, and enhancing cancer stemness and tumorigenesis [85]. 4.6. miR-203 In CRC, miR-203 plays opposing roles in different stages. For example, the serum miR-203 level of stage IIICIV patients is higher than that of stage ICII patients [86] In the CRC cell lines HCT-116 and HT-29, miR-203 acts as a tumor suppressor to suppress tumorsphere formation, self-renewal ability, CSC migration, and the expression of stem markers via direct inhibition of GATA-binding protein 6 (GATA6). GATA6, which belongs to a small family of zinc finger transcription factors, is responsible for normal intestinal epithelium proliferation and maturation [87], CRCs self-renewal ability, and invasion [88,89]. In CSCs, GATA6 downregulates dickkof-1 (DKK-1), which is a negative effector of the Wnt/-catenin pathway and upregulates LGR5 Ned 19 to activate the Wnt/-catenin pathway. In short, miR-203 inhibits CRC stemness by suppressing GATA6 and activation of the Wnt/-catenin pathway, indicating that it might contribute to CRC clinical diagnosis and therapy [90]. 4.7. miR-139-5p In the HCT-116 and HT-29 cell lines, miR-139-5p suppress CSCs self-renewal, tumorsphere formation, tumor metastasis, and recurrence as well as stem maker expression via inhibition of transcription factor 4 (TCF4, also known as E2-2). E2-2 is a basic helix-loop-helix (bHLH) transcription factor of transcription factor 7-like 2 (TCF7L2), which initiates downstream factors of the Wnt/-catenin pathway. In CRC, the overexpression of E2-2 leads to hyperactivation of the Wnt/-catenin pathway, contributing to tumor survival and development [91]. Moreover, E2-2 plays a crucial role in promoting EMT [92]. Notably, E2-2 could be stimulated by external factors to regulate the Wnt/-catenin pathway reversely. Therefore, by inhibiting E2-2 expression at the protein level, miR-139-5p attenuates CSC stemness, and inhibits tumor metastasis and development [93]. 4.8. miR-221 In the CRC cell line HCT-116, the overexpression of miR-221 enhances CSCs self-renewal and tumorsphere formation ability, increases the expression of stem markers, and suppresses apoptosis by inhibiting Quaking-5 (QKI-5). RGS17 QKI-5 is the most abundant isoform of QKI and its presence always indicates good prognosis for patients [94]. Additionally, the reduction of QKI is important for CRC development and the stemness maintenance of both normal stem cells and CSCs [95,96]. Moreover, QKI-5 is involved in EMT regulation as well [97]. miR-221 attenuates the suppressive effect of QKI-5 on CSCs to facilitate enlargement of the CSC population and tumorigenesis. As a result, overexpression of miR-221 indicates poor prognosis and a lower life expectancy overall success price [98] usually. 5..