Downregulated let-7d positively stimulates rectum adenocarcinoma cell malignant biological behaviors by upregulating ATP binding cassette subfamily C member 2

Zhen-Ji Liu, Yuan-Yuan Ma, Tong-Ming Liu, Jian-Xin Wang, Li Zhang, Lei Jin, Miao Yu, Hua-Long Yu


Background: Let-7d has been reported to serve as a tumor suppressor in numerous cancers, however, the function in rectum adenocarcinoma has not been illuminated. In this study, we aimed to explore whether let-7d functions in rectum adenocarcinoma and its functional significance links to ATP binding cassette subfamily C member 2 (ABCC2).
Methods: The expression patterns of let-7d and ABCC2 were gained from TCGA database. Then, cell proliferation, invasion and migration assays were conducted to detect the influence on rectum adenocarcinoma cells behaviors after over-expression of let-7d. Subsequently, the potential target gene of let-7d was predicted and identified through bioinformatics prediction analysis and luciferase reporter assay. Analyses against prognostic value and independent predictor were acquired from Kaplan-Meier, Univariate and Multivariate analysis of Cox regression. Finally, con-transfection experiments were performed to investigate let-7d/ABCC2 pairs function on rectum adenocarcinoma cells after co-transfected with let-7d mimic and si-ABCC2. mRNA and protein levels were assessed by reverse transcription quantitative polymerase chain reaction (qRT-PCR) and western blot.
Results: The data from TCGA indicated that let-7d was down-regulated in rectum adenocarcinoma samples, whilst ABCC2 was showed a trend of high expression and its overexpression hinted to worse overall survival of rectum adenocarcinoma patients. Cells proliferation, invasion and migration properties were restrained after over-expression of let-7d in SW837 cells. Further investigations showed that over-expression of let-7d induced the inhibitory effect on SW837 cells proliferative, migrant and invasive capacities was augmented by silencing ABCC2.
Conclusions: All results in this study indicated that up-regulation of let-7d could suppress SW837 cells growth, invasion and migration abilities by reducing ABCC2 expression, providing a new insight into molecular mechanism of let-7d/ABCC2 as a significant mediator for tumor progression and development of rectum adenocarcinoma.