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Tumour Biol. 2016 Jul;37(7):8931-40. doi: 10.1007/s13277-015-4771-6. Epub 2016 Jan 11.

Down-regulation of miR-320 associated with cancer progression and cell apoptosis via targeting Mcl-1 in cervical cancer.

Author information

1
Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, 214002, China. zhangting040715@163.com.
2
Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment Cancer Center; School of Public Health, Nanjing Medical University, Nanjing, 210029, China. zhangting040715@163.com.
3
Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, 214002, China.
4
Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment Cancer Center; School of Public Health, Nanjing Medical University, Nanjing, 210029, China. jwzhou@njmu.edu.cn.

Abstract

Our previous studies have demonstrated overexpression of Mcl-1 in cervical cancer tumorigenesis. However, the molecular mechanism of its overexpression remains not elucidated. MiR-320 has been reported to be down-regulated in various types of cancer, and bioinformatics prediction indicated that it may regulate the expression of Mcl-1. The aim of this study is to investigate the role of miR-320 and its target gene Mcl-1 in cervical cancer progression and to assess their clinical significance. miR-320 and Mcl-1 expressions in human cervical cancer tissues were investigated by qRT-PCR, in situ hybridization, and immunohistochemical staining, respectively. The clinicopathological implications of these molecules were analyzed. Bioinformatic prediction and luciferase assays were employed to identify the predicted microRNA (miRNA) which regulates Mcl-1. The apoptosis, proliferation, migration, and invasion assays were performed to investigate the effect of miR-320 on the cervical cancer cells. MiR-320 expression is significantly down-regulated versus Mcl-1 expression is up-regulated in cervical cancer tissues compared with normal controls with a negative correlation between them. Luciferase assay showed that miR-320 negatively regulates Mcl-1 expression. In addition, miR-320 induces apoptosis via down-regulation of Mcl-1 and activation of caspase-3 but inhibits cell proliferation, migration, invasion, and tumorigenesis in cervical cancer cells. Our studies show that miR-320 expression is decreased in cervical cancer, and its expression is negatively correlated with Mcl-1 expression in cervical cancer. In addition, miR-320 inhibits cervical cancer progression by down-regulation of Mcl-1. These results indicate that miR-320 may be an important biomarker and target for diagnosis and treatment of cervical cancer patient.

KEYWORDS:

Apoptosis; Cervical cancer; Mcl-1; miR-320

PMID:
26753959
DOI:
10.1007/s13277-015-4771-6
[Indexed for MEDLINE]

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