The advances of E2A-PBX1 fusion in B-cell acute lymphoblastic Leukaemia.

The E2A-PBX1 gene fusion is a common translocation in B-cell acute lymphoblastic leukaemia. Patients harbouring the E2A-PBX1 fusion gene typically exhibit an intermediate prognosis. Furthermore, minimal residual disease has unsatisfactory prognostic value in E2A-PBX1 B-cell acute lymphoblastic leukaemia. However, the mechanism of E2A-PBX1 in the occurrence and progression of B-cell acute lymphoblastic leukaemia is not well understood. Here, we mainly review the roles of E2A and PBX1 in the differentiation and development of B lymphocytes, the mechanism of E2A-PBX1 gene fusion in B-cell acute lymphoblastic leukaemia, and the potential therapeutic approaches.

CircMYH9 increases KPNA2 mRNA stability to promote hepatocellular carcinoma progression in an EIF4A3-dependent manner.

Hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer worldwide with a high incidence of recurrence and metastasis; however, the molecular mechanisms underlying HCC development remain to be fully understood. In this study, we identified circMYH9 as an important regulator of HCC. Overexpression of circMYH9 induced, while knockdown of circMYH9 inhibited, the proliferation, migration, and invasion of HCC cells. Mechanistically, circMYH9 bound to eukaryotic translation initiation factor 4A3 (EIF4A3) and increased karyopherin subunit alpha 2 (KPNA2) mRNA stability. circMYH9 knockdown in HCC cells reduced the stability of KPNA2 mRNA. Importantly, circMYH9 regulation of HCC required the activity of KPNA2. In support with this, circMYH9 level was positively correlated with the expression of KPNA2 in HCC patient samples. Taken together, our study was the first to uncover the oncogenic role of circMYH9 in HCC and further elucidated the functional mechanism of circMYH9 by interacting with EIF4A3 to increase KPNA2 mRNA stability. Our findings might provide a novel potential target for the diagnose and treatment of HCC.

Exosomal circRNA HIPK3 knockdown inhibited cell proliferation and metastasis in prostate cancer by regulating miR-212/BMI-1 pathway.

Prostate cancer (PCa) is the second frequent malignancy among men in the world. Exosomal circular RNAs (circRNAs) have been reported to function in PCa progression. The current study aimed to investigate the role of exosomal circRNA homeodomain-interacting protein kinase 3 (circHIPK3) in PCa development. Exosomes were extracted from serum and cells utilizing commercial kit, and identified by transmission electron microscopy (TEM), Western blot assay and nanoparticle tracking analyzer. Relative expression of circHIPK3, microRNA (miR)-212 and B-cell specific MMLV insertion site-1 (BMI-1) was examined by quantitative realtime PCR or Western blot assay. Receiver Operating Characteristic (ROC) analysis was conducted to assess the diagnostic potential of exosomal miR-212. Cell viability, and metastasis including migration and invasion, were detected by Methyl thiazolyl tetrazolium (MTT) assay and Transwell assay, respectively. Cell apoptosis was monitored using flow cytometry. The interaction between miR-212 and circHIPK3 or BMI-1 was validated by dual-luciferase reporter assay. Xenograft tumor assay was employed to explore the role of exosomal circHIPK3 in vivo. Exosomal circHIPK3 was increased in serum of PCa patients, and could discriminate PCa patients from normal volunteers. Depletion of exosomal circHIPK3 or overexpression of exosomal miR-212 reduced viability, migration and invasion, but promoted cell apoptosis in PCa cells, which was attenuated by miR-212 inhibition or BMI-1, respectively. MiR-212 targeted BMI-1, and downregulated BMI-1 expression. Exosomal circHIPK3 knockdown also suppressed tumor growth in vivo. Exosomal circHIPK3 knockdown inhibited PCa progression by regulating miR-212/BMI-1 axis, at least in part, offering a new insight into the molecular mechanism of PCa.

Early visual quality outcomes after small-incision lenticule extraction surgery for correcting high myopic astigmatism.

BACKGROUND: To evaluate early optical quality outcomes after small-incision lenticule extraction (SMILE) surgery for correcting high myopic astigmatism. METHODS: This retrospective study enrolled 55 eyes from 37 patients who had preoperative myopic astigmatism of ≥2.00 diopters (D) who had been treated with SMILE surgery. Preoperatively, the mean cylinder was - 2.41 ± 0.54 D (range, - 2.00 D to - 4.50 D). The preoperative and postoperative visual outcomes, refraction, and higher-order aberration (HOA) at 1 and 3 months were compared. Refractive astigmatism changes were analyzed by the Alpins vector method. RESULTS: Three months after SMILE surgery, the average cylinder was - 0.14 ± 0.31 D, and the average astigmatism vector was - 0.09 D × 6.34°. The angle of error (AofE) was limited to within ±10°, and the magnitude of error was limited to within ±1.0 D in all patients. The correction index (CI) was 0.98 ± 0.07, the index of success (IOS) was 0.08 ± 0.13, and the flattening index (FI) was 0.97 ± 0.07. Significant positive correlations were found between IOS and |AofE| (P = 0.000); negative correlations were found between FI and |AofE| (P = 0.000). The postoperative total HOA, spherical aberration, vertical coma aberration, and trefoil 30° were increased significantly compared with preoperative measurements, and the increase in HOA was closely related to preoperative astigmatism (P < 0.05). CONCLUSIONS: SMILE has preferable outcomes for correcting high myopic astigmatism. Axis rotation during the surgery might influence the undercorrection of astigmatism. The increase of HOA after surgery is related to preoperative astigmatism.

Dynamics and cooperativity of Trp-cage folding.

In this study, multiple independent molecular dynamics (MD) simulations on Trp-cage folding were performed at 300, 325 and 375 K using generalized Born (GB) implicit solvent model. The orientational movement of the side-chain of Trp6 to form a hydrophobic core with 3(10)-helix was observed. The breaking/formation of a salt bridge between Asp9 and Arg16 was proposed to be the prerequisite for Trp-cage folding/refolding. Our results demonstrate that the cooperation between the salt bridge and the Trp6 orientation leads to a stable tertiary structure of Trp-cage. Analyses on backbone concerted motions at different temperatures indicate that interactions between Trp6 and 3(10)-helix & Pro18 and between Pro12 and Pro17 & Pro18 are weakened at 375 K but strengthened at lower temperatures, suggesting that they could be the potential driving force of hydrophobic collapse.