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

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.

• Authors: Ye Lei, Bin Li, Shiyu Tong, Lin Qi, Xiheng Hu, Yunbo Cui, Zengbo Li, Wei He, Xiongbing Zu, Zhi Wang, Minfeng Chen
• Journal: PloS one (PLoS One) Vol. 10 Issue 2 Pg. e0117809 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25658842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• Antineoplastic Agents
• MIRN101 microRNA, human
• MicroRNAs
• Vascular Endothelial Growth Factor C
• Luciferases
• Cisplatin

Topics

• 3' Untranslated Regions (genetics)
• Antineoplastic Agents (pharmacology)
• Base Sequence
• Blotting, Western
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Survival (drug effects, genetics)
• Cisplatin (pharmacology)
• Gene Expression Regulation, Neoplastic
• HEK293 Cells
• Humans
• Luciferases (genetics, metabolism)
• MicroRNAs (genetics)
• Microscopy, Fluorescence
• Molecular Sequence Data
• Mutation
• Neoplasm Invasiveness
• RNA Interference
• Reverse Transcriptase Polymerase Chain Reaction
• Urinary Bladder Neoplasms (genetics, metabolism, pathology)
• Vascular Endothelial Growth Factor C (genetics, metabolism)