RETRACTED ARTICLE: N6-methyladenosine induced miR-143-3p promotes the brain metastasis of lung cancer via regulation of VASH1

Hongsheng Wang,Qianqian Deng,Ziyan Lv,Yuyi Ling,Xue Hou,Zhuojia Chen,Xiaoxiao Dinglin,Shuxiang Ma,Delan Li,Yingmin Wu,Yanxi Peng,Hongbing Huang,Likun Chen

doi:10.1186/s12943-019-1108-x

Abstract

BackgroundBrain metastasis (BM) is one of the principal causes of mortality for lung cancer patients. While the molecular events that govern BM of lung cancer remain frustrating cloudy.MethodsThe miRNA expression profiles are checked in the paired human BM and primary lung cancer tissues. The effect of miR-143-3p on BM of lung cancer cells and its related mechanisms are investigated.ResultsmiR-143-3p is upregulated in the paired BM tissues as compared with that in primary cancer tissues. It can increase the invasion capability of in vitro blood brain barrier (BBB) model and angiogenesis of lung cancer by targeting the three binding sites of 3’UTR of vasohibin-1 (VASH1) to inhibit its expression. Mechanistically, VASH1 can increase the ubiquitylation of VEGFA to trigger the proteasome mediated degradation, further, it can endow the tubulin depolymerization through detyrosination to increase the cell motility. m6A methyltransferase Mettl3 can increase the splicing of precursor miR-143-3p to facilitate its biogenesis. Moreover, miR-143-3p/VASH1 axis acts as adverse prognosis factors for in vivo progression and overall survival (OS) rate of lung cancer.ConclusionsOur work implicates a causal role of the miR-143-3p/VASH1 axis in BM of lung cancers and suggests their critical roles in lung cancer pathogenesis.

Highlights

Brain metastasis (BM), which occurs in 20–40% of advanced stage cancers, is one of the most common adult intracranial malignancies [1]
Among the upregulated miRNAs, only miR-27b, miR-143-3p, and miR-145 were upregulated in each BM tissue as compared to that in the matched primary lung cancer tissues (Additional file 1: Figure S1A, B, C)
We checked the expression of miR-27b, miR-143-3p, miR-145, and miR-192 in primary lung cancer tissues with (n = 10) or without (n = 10) BM by in situ hybridization (ISH)

Summary

Introduction

Brain metastasis (BM), which occurs in 20–40% of advanced stage cancers, is one of the most common adult intracranial malignancies [1]. Clinical management of BM patients with cancer has limited control efficiency. The survival times after BM diagnosis of cancer patients remain poor and less than 12 months [2]. Lung cancer is the most common primary site for secondary BM [3]. BM is identified in about 10% of all lung cancer patients [4]. Brain metastasis (BM) is one of the principal causes of mortality for lung cancer patients. While the molecular events that govern BM of lung cancer remain frustrating cloudy

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