ncRNA basic information
ncRNA ID:
MI0000242/MI0000281
ncRNA Database:
miRBase
ncRNA Name:
miR-199a
ncRNA Type:
miRNA
ncRNA Expression:
up-regulated
ncRNA Method:
qRT-PCR
ncRNA Target Gene:
GSK3Beta
ncRNA Pathway:
Wnt/Beta-catenin pathway
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00515 (APRD00359)
Drug Name:
Cisplatin
Drug Method:
The aim of this study was to investigate the biological function of miR-199a/b on cisplatin resistance in colorectal cancer stem cells and its related mechanisms. Here, ALDHA1+ cells from primary colorectal cancer tissues behaved similar to cancer stem cells and were chemoresistant to cisplatin. The presence of a variable fraction of ALDHA1 was detected in 9 out of 10 colorectal cancer specimens. Significantly, increased miR-199a/b expression was detected in ALDHA1+ colorectal cancer stem cells, accompanied by a downregulation of Gsk3 and an overexpression of catenin and ABCG2. In patient cohort, enhanced miR-199a/b expression in colorectal cancer tissues was associated with cisplatin response and poor patient survival. In addition, 80% of colorectal cancer samples showed lower level of Gsk3 than their adjacent normal counterparts. Furthermore, Gsk3 was the direct target of miR-199a/b. MiR-199a/b regulated Wnt/catenin pathway by targeting Gsk3 in ALDHA1+ colorectal cancer stem cells. By blocking Wnt/catenin pathway, we implied that ABCG2 lies downstream of Wnt/catenin pathway. ABCG2 was further demonstrated to contribute cisplatin resistance in ALDHA1+ colorectal cancer stem cells and can be regulated by miR-199a/b. Thus, our data suggested that upregulation of miR-199a/b in ALDHA1+ colorectal cancer stem cells contributed to cisplatin resistance via Wnt/catenin-ABCG2 signaling, which sheds new light on understanding the mechanism of cisplatin resistance in colorectal cancer stem cells and facilitates the development of potet of potential therapeutics againstainst colorectal cancer.
Drug Response:
resistant
Cancer basic information
Cancer:
colorectal cancer
Tissue/Cell:
cell line
Other information
Title:
Upregulation of miR-199a/b contributes to cisplatin resistance via Wnt/Beta-catenin-ABCG2 signaling pathway in ALDHA1+ colorectal cancer stem cells.
Journal:
Tumour Biol
Published:
2017
PubMed ID:
28639895