Impaired DICER1 function promotes stemness and metastasis in colon cancer

Abstract

Disruption of microRNA (miRNA) expression patterns is now being recognized as a hallmark of human cancer. The causes of these altered profiles are diverse, and, among them, we found the existence of defects in the miRNA processing machinery. However, little is known about how these alterations affect the biology of the underlying tumors. Herein, we show that colorectal cancer cells with an impairment in DICER1, a major miRNA biogenesis gene, undergo enrichment of tumor stemness features and an epithelial-to-mesenchymal transition. These phenotypes are associated with the downregulation of miRNAs, such as miR-34a, miR-126 and those of the miR-200 family, that target critical coding genes in these pathways. Most importantly, DICER1 impairment also induces the acquisition of a greater capacity for tumor initiation and metastasis, two properties associated with cancer stem cells.

Dicer Elicits Paclitaxel Chemosensitization and Suppresses Cancer Stemness in Breast Cancer by Repressing AXL

“…1C). Dicer-impaired colon cancer cells have enhanced cancer stem cell features and metastasis (22). Therefore, we examined whether the upregulation of Dicer by E1A created a shift in the pattern of expression of breast cancer stem cell properties.…”

“…Recent studies indicate that Dicer may act as a tumor suppressor for cancer stemness, metastasis, and tumor progression (22,38). However, it is still unclear whether Dicer expression and paclitaxel sensitivity in breast cancer are correlated.…”

“…Accumulating studies have shown that downregulation of Dicer is associated with cancer progression in breast cancer (17)(18)(19)(20), hepatocellular carcinoma (21), colon cancer (22), and ovarian cancer (23). However, the underlying molecular mechanisms of Dicer regulation and chemotherapeutic sensitization in breast cancer are not fully understood.…”

Mutual regulation of microRNAs and DNA methylation in human cancers

“…10,11 Colorectal cancer cells with defects on Dicer1 showed enrichment of tumor stemness features and an epithelial-mesenchymal transition (EMT), leading to the downregulation of miR-34a, miR-126, and miR-200 family and the acquisition of a greater capacity for tumor initiation and metastasis. 12 These findings indicate that miRNA machinery genes contribute to cancer development and progression.…”

Osteosarkoma pediatrikoarekiko suszeptibilitatean inplikatuta dauden aldaera genetikoak

“…Adibidez, ez dira berdin adierazten minbizian: esate baterako, EIF2C2 genea (AGO konplexuan) eta TARBP2 genea (DICER konplexuan) gain-adierazita daude prostatako minbizian; DROSHA eta DICER geneak, ostera, azpi-adierazita bularreko minbizian [28]. Gainera, zenbait ikerketa-lanetan ikusi denez, prozesamendu-gene horietan adierazpen-aldaketak gertatzen direnean, aldaketa horiek eragina izaten dute miRNA ekoizpenean [29][30][31][32], eta minbizian gertatzen den gene-adierazpena alda dezakete. Ondorioz, miRNAen prozesamendu-geneetan dauden SNPek miRNAen funtzioa alda dezakete.…”