RETRACTED ARTICLE: N6-methyladenosine induced miR-143-3p promotes the brain metastasis of lung cancer via regulation of VASH1

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.

Downregulation of m6A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non‐small cell lung cancer

“…21 Another m 6 A methyladenosine METTL3 (m 6 A writer) induced miR-143-3p has been reported to promote the brain metastasis of lung cancer via regulation of VASH1. 22 In addition, Liu et al demonstrated that m 6 A demethylase FTO (m 6 A eraser) promotes cell proliferation and invasion in lung squamous cell carcinoma by regulating MZF1 expression. 23 However, m 6 A binding proteins (m 6 A readers) remain unexplored in NSCLC.…”

Novel insights into the interplay between m6A modification and noncoding RNAs in cancer

“…METTL3 facilitates the maturation of pri-miR-1246 to enhance the metastasis of colorectal cancer (CRC) [49]. METTL3 also accelerates the maturation of miR-143-3p, leading to the formation of METTL3/miR-143-3p/vasohibin-1 axis to favor the metastasis of lung cancers [50].…”

The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients

“…MiR-143-3p was identified as the key specific mediator of KIAA1429 expression in osteosarcoma cells [36]. In addition, it is also involved in the regulation of cell proliferation in cervical cancer, esophageal cancer, breast cancer, lung cancer and other neoplasms [37][38][39][40]. MiR19b-3p has also been implicated in the pathogenesis of several cancers in humans [41,42].…”