No abstract

Exportin 5 (XPO5) is a shuttle protein that mediates precursor miRNA (pre‐miRNA) export from the nucleus to the cytoplasm, an important step in miRNA maturation. We previously demonstrated that XPO5 was phosphorylated by ERK kinase and subsequently underwent conformation change by the peptidyl‐prolyl isomerase Pin1, leading to the reduced miRNA expression in hepatocellular carcinoma (HCC). Protein phosphorylation modification serves as a reversible regulatory mechanism precisely governed by protein kinases and phosphatases. Here we identified that the phosphatase PP2A catalyzed XPO5 dephosphorylation. PP2A holoenzyme is a ternary complex composed of a catalytic subunit, a scaffold subunit, and a regulatory subunit that determines substrate specificity. In this study, we characterized the involvement of B55β subunit in XPO5 dephosphorylation that favored the distribution of XPO5 into the cytoplasm and promoted miRNA expression, leading to HCC inhibition in vitro and in vivo. Our study demonstrates the regulatory role of B55β‐containing PP2A in miRNA expression and may shed light on HCC pathogenesis.

BackgroundThe clinical application of coronary MR angiography (MRA) remains limited due to its long acquisition time and often unsatisfactory image quality. A compressed sensing artificial intelligence (CSAI) framework was recently introduced to overcome these limitations, but its feasibility in coronary MRA is unknown.PurposeTo evaluate the diagnostic performance of noncontrast‐enhanced coronary MRA with CSAI in patients with suspected coronary artery disease (CAD).Study TypeProspective observational study.PopulationA total of 64 consecutive patients (mean age ± standard deviation [SD]: 59 ± 10 years, 48.4% females) with suspected CAD.Field Strength/SequenceA 3.0‐T, balanced steady‐state free precession sequence.AssessmentThree observers evaluated the image quality for 15 coronary segments of the right and left coronary arteries using a 5‐point scoring system (1 = not visible; 5 = excellent). Image scores ≥3 were considered diagnostic. Furthermore, the detection of CAD with ≥50% stenosis was evaluated in comparison to reference standard coronary computed tomography angiography (CTA). Mean acquisition times for CSAI‐based coronary MRA were measured.Statistical TestsFor each patient, vessel and segment, sensitivity, specificity, and diagnostic accuracy of CSAI‐based coronary MRA for detecting CAD with ≥50% stenosis according to coronary CTA were calculated. Intraclass correlation coefficients (ICCs) were used to assess the interobserver agreement.ResultsThe mean MR acquisition time ± SD was 8.1 ± 2.4 minutes. Twenty‐five (39.1%) patients had CAD with ≥50% stenosis on coronary CTA and 29 (45.3%) patients on MRA. A total of 885 segments on the CTA images and 818/885 (92.4%) coronary MRA segments were diagnostic (image score ≥3). The sensitivity, specificity, and diagnostic accuracy were as follows: per patient (92.0%, 84.6%, and 87.5%), per vessel (82.9%, 93.4%, and 91.1%), and per segment (77.6%, 98.2%, and 96.6%), respectively. The ICCs for image quality and stenosis assessment were 0.76–0.99 and 0.66–1.00, respectively.Data ConclusionThe image quality and diagnostic performance of coronary MRA with CSAI may show good results in comparison to coronary CTA in patients with suspected CAD.Evidence Level1.Technical Efficacy2.