Abstract
AbstractIdentifying agents that inhibit the proliferation of cancer stem cells is of great importance in cancer biology. Curcumin has been shown to function as an anti-cancer agent. One of the tumor suppressors that appear to be induced in response to curcumin treatment is p53. A recent study suggests that curcumin increases the expression of miRNAs, such as miR-22, miR-181a, b, c, miR-34, miR-103, and miR-21. Intriguingly, miR-34, 181b, c, miR-103, miR-21, and miR-24 have been identified as transcriptional targets of the tumor suppressor p53. This data suggests a possibility that curcumin, by inducing the expression of p53, it could increase the expression of these microRNAs. A number of groups have shown that c-Myc, Sox-2, Klf-4, Oct-4, Sox-2, Nanog, and Lin28 are required for reprogramming of differentiated cells into pluripotent stem cells and for cancer stem cell proliferation. Interestingly, miR-21 has recently been shown to represses stem cell factors such as Oct4, Nanog, sox2, and c-Myc, indicating that curcumin by increasing the expression of miR-21, it could inhibit cancer stem cell proliferation. In addition, curcumin induced p53 may result in increased expression of its target, miR-145. Interestingly, it has recently been shown that miR-145 suppresses the expression of c-myc, klf-4, Oct-4, and Sox-2 in human embryonic stem cells (hESCs) and thereby promotes the differentiation of hESC. This data suggests that p53-dependent miR-145 expression will result in down regulation of Oct-4, Klf-4, Sox-2, Nanog, and c-myc and inhibition of stem cell proliferation. Further, curcumin induced miR-22 appears to inhibit the expression of estrogen receptor α. Remarkably, it has recently been shown that estrogen receptor α inhibits the processing of several microRNAs, including the tumor suppressor miR-145. This data suggests that curcumin, by inhibiting the expression of estrogen receptor α. through its target miR-22, it could increase the processing of miR-145 and down regulate the expression of its target genes (Oct-4, Klf-4, Sox-2, Nanog, and c-myc). Thereby, curcumin could function as a positive regulator of miRNA processing and a negative regulator of cancer stem cell proliferation.
Highlights
Identifying agents that inhibit the proliferation of stem cells is of great importance in regenerative medicine
Identifying agents that increase the expression of miRNAs to inhibit cancer stem cell (CSC) proliferation is of great importance in cancer biology
Curcumin- a) induced miR-15/16a appears to inhibit the expression of the negative regulator of INK4a/ARF, BMI; and b) inhibited NFKB activity appears to inhibit the expression of lin-28 and thereby induce the tumor suppressor let-7 expression
Summary
Identifying agents that inhibit the proliferation of stem cells is of great importance in regenerative medicine. Identifying agents that increase the expression of miRNAs to inhibit cancer stem cell (CSC) proliferation is of great importance in cancer biology. I propose for the first time that Curcumin: a) inhibits CSCs proliferation; and b) increases miRNA processing.
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