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PLoS One. 2015 Feb 6;10(2):e0117809. doi: 10.1371/journal.pone.0117809. eCollection 2015.

miR-101 suppresses vascular endothelial growth factor C that inhibits migration and invasion and enhances cisplatin chemosensitivity of bladder cancer cells.

Author information

1
Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.
2
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, Hebei, 050017, China.
3
School of Life Sciences, Central South University, No. 110 Xiangya Road, Changsha, Hunan, 410008, China.
4
Department of General Surgery, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.

Abstract

BACKGROUND:

The microRNA miR-101 is downregulated in several cancers, including bladder cancer. However, miR-101's role in the invasion, metastasis, and chemosensitivity of bladder cancer cells remains unclear. This study was conducted to determine miR-101's role on the lymphangiogenic molecule vascular endothelial growth factor C (VEGF-C) and their effects upon bladder cancer cell migration, invasion, and chemosensitivity to cisplatin.

METHODS:

Two bladder cancer cell lines (T24 and 5637) and the tool cell line 293T were employed here. Bladder cancer cells were transfected with either a miR-101 overexpression vector or a scrambled-sequence lentivirus, both of which exhibited a high transfection efficiency. Non-transfection was used as a mock negative control. Wound healing and Transwell assays were performed to measure cell migration and invasiveness. A luciferase reporter assay was performed to validate miR-101's interaction with VEGF-C's 3' untranslated region followed by RT-PCR and Western blot confirmation. An MTS assay was used to evaluate the cisplatin sensitivity of the cell lines.

RESULTS:

miR-101 overexpression significantly inhibited the migration and invasiveness while significantly enhancing cisplatin sensitivity. miR-101 negatively regulated VEGF-C protein expression, and VEGF-C overexpression rescued the effects of miR-101 overexpression, indicating that miR-101 negatively regulates VEGF-C protein expression post-transcriptionally. miR-101 and VEGF-C interference independently enhanced cisplatin cytotoxicity in bladder cancer cells.

CONCLUSIONS:

miR-101 suppresses VEGF-C expression, inhibits cell migration and invasion, and increases cisplatin sensitivity in bladder cancer cells. This study provides new insight into miR-101's role in bladder cancer and shows miR-101's promise as a potential molecular target for bladder cancer.

PMID:
25658842
PMCID:
PMC4320037
DOI:
10.1371/journal.pone.0117809
[Indexed for MEDLINE]
Free PMC Article

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