Journal
EXPERIMENTAL AND MOLECULAR PATHOLOGY
Volume 104, Issue 1, Pages 98-107Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yexmp.2018.01.006
Keywords
Colorectal cancer; miR-142-5p; KLF6; Targeted therapy; Onco-miRNA
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Funding
- Griffith University
- Menzies Health Institute Queensland
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Objectives: miR-142-5p was noted aberrantly expressed and plays important roles in different pathophysiological conditions in human. The present study aims to examine the expression of miR-142-5p and its association with clinicopathological factors in a large cohort of patients with colorectal cancer. In addition, the cellular effects of miR-142-5p and its interacting targets in colon cancer cells were investigated. Methods: Expression of miR-142-5p in colorectal cancer tissues (n = 125) and colon cancer cell lines were analysed using real-time polymerase chain reaction. In vitro assays (cell proliferation, wound healing and colony formation) were used to study the miR-142-5p induced cellular effects. Western blots were used to examine the modulation of FAM134B, KRAS, EPAS1 and KLF6 proteins expression followed by miR-142-5p expression-manipulation. Results: Significant high expression of miR-142-5p was noted in cancer tissues and cells when compared to the controls (p < 0.001). Overexpression of miR-142-5p in patients with colorectal cancer was common (72%; 90/125). miR-142-Sp overexpression was associated with cancer in the proximal colorectum and with B-ref positive patients (p = 0.05). Exogenous overexpression of miR-142-5p resulted in significantly increased cell proliferation, colony formation, and wound healing capacities, whereas inhibition of endogenous miR-142-5p led reduced cancer growth properties. The cellular effects of miR-142-5p were mediated by the modulation of tumour suppressor KLF6 expression, as the expression of miR-142-5p and KLF6 protein are inversely correlated in colon cancer cells. Conclusion: High miR-142-5p expression was associated with the biological aggressiveness of cancer. Thus, suppression of miR-142-5p could be a therapeutic strategy for patients with colorectal cancers.
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