MiR-489-3p inhibits proliferation and migration of bladder cancer cells through downregulation of histone deacetylase 2.

Dan Sun,Jiaxing Lin,Meng Yu,Xin Meng,Haotian Xin,Jieping Yang,Tianren Li,Toshinori Ozaki,Yuyan Zhu,Jun An,Biao Wang

doi:10.3892/ol.2020.11869

Abstract

Since human bladder cancer (BC) is a common malignancy of the urinary system with poor prognosis, it is crucial to clarify the molecular mechanisms of BC development and progression. To the best of our knowledge, the current study demonstrated for the first time that miR-489-3p suppressed BC cell-derived tumor growth in vivo via the downregulation of histone deacetylase 2 (HDAC2). According to the results, expression levels of miR-489-3p were lower in BC tissues compared with corresponding normal tissues. Expression of miR-489-3p mimics in BC-derived T24 and 5637 cells resulted in a significant reduction in proliferation and migration rates. Furthermore, bioinformatics analyses indicated that HDAC2 may be a potential downstream target of miR-489-3p. In contrast to miR-489-3p, HDAC2 was expressed at higher levels in BC tissues compared with corresponding normal tissues. Additionally, small interfering RNA-mediated knockdown of HDAC2 caused a marked decrease in the proliferation and migration rates of T24 and 5637 cells. Consistent with these observations, expression of miR-489-3p mimics attenuated the growth of xenograft tumors arising from T24 cells and resulted in HDAC2 downregulation. In conclusion, the results of the current study indicated that the miR-489-3p/HDAC2 axis serves a role in the development and/or the progression of BC and may be a potential molecular target for the development of a novel strategy to treat patients with BC.

Highlights

Bladder cancer (BC) is the most frequently diagnosed malig‐ nancy of the urinary system
The expression levels of miR‐489‐3p in 11 BC tumor tissues and their corresponding normal tissues were measured by reverse transcription‐quantitative PCR (RT‐qPCR) to determine the potential role of miR‐489‐3p in the regulation of human BC. miR‐489‐3p was expressed at lower levels in BC tumor tissues compared with corre‐ sponding adjacent normal tissues, indicating that miR‐489‐3p may exhibit anti‐tumor capabilities against BC (Fig. 1A)
At 48 h post‐transfection, miR‐489‐3p expression levels were determined by RT‐qPCR. miR‐489‐3p expression levels were significantly increased in T24 cells transfected with miR‐489 mimics/agomirs and significantly decreased in cells trans‐ fected with miR‐489‐3p inhibitors/antagomirs compared with their corresponding negative control (NC) (Fig. 1B and C). 5367 cells exhibited similar results

Summary

Introduction

Bladder cancer (BC) is the most frequently diagnosed malig‐ nancy of the urinary system. >70% of newly diagnosed patients with BC exhibit non‐muscle invasive BC and ~50‐70% of these cases eventually exhibit invasive potential with more aggressive characteristics [2]. The standard treatment choice for patients with BC is primarily surgical resection. Patients with BC undergoing surgery are at high‐risk of the recurrence, as well as occasional stage progression. In advanced BC, following radical surgery or radiotherapy, patients still have poor outcomes [3]. The therapeutic effects in patients with BC remain poor [4]. It is crucial to elucidate the molecular mechanisms of the malignant properties of BC to increase the survival times of patients and provide novel strategies and/or molecular targets for the early diagnosis and more effective treatment of patients with BC

Methods

Results

Conclusion