Journal
ONCOTARGET
Volume 7, Issue 3, Pages 2660-2671Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6545
Keywords
miR-497; colorectal cancer; KSR1; tumorigenesis; chemosensitivity
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Funding
- National Natural Science Foundation of China [81472944, 81320108019, 81302182, 81270736]
- Huai'an Science and Technology Bureau [HAS2013021]
- Science and Technology Department of Jiangsu Province [BRA2014129]
- National Institutes of Health [R01ES020868, R01CA193511]
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Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Recently, downregulation of microRNA-497 (miR-497) has been observed in CRC tissues. In this study, we found that miR-497 expression levels were downregulated in human CRC specimens compared to the adjacent normal tissues. MiR-497 expression levels were strongly correlated with clinical stages and lymph node metastases. Furthermore, kinase suppressor of ras 1 (KSR1), a known oncogene, was a direct target of miR-497, and KSR1 expression levels were inversely correlated with miR-497 expression levels in human CRC specimens. Overexpression of miR-497 inhibited cell proliferation, migration, invasion and increased chemosensitivity to 5-fluorouracil treatment, whereas forced expression of KSR1 had the opposite effect. Taken together, these results revealed that lower miR-497 levels in human CRC tissues induce KSR1 expression which is associated with CRC cancer occurrence, advanced stages, metastasis and chemoresistance. Lower miR-497 levels may be a potential biomarker for CRC advanced stages and treatment response.
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