Nasal natural killer (NK) cell lymphoma (NNL) is an Epstein-Barr virus-associated lymphoma of cytotoxic NK cell origin. The Epstein-Barr virus-encoded miR-BART20-5p inhibits T-bet (TBX21), the master transcription factor of cytotoxic NK cells. To further explore the roles of miRNAs in NNLs, we measured the miRNA expression profiles of 36 NNLs. miR-21, miR-142-3p, miR-126, miR-451, and miR-494-3p were the top five miRNAs with the highest expression levels. By using pathway analysis, we identified associations between all of the five miRNAs with the PTEN-AKT-mTOR pathway, in which PTEN suppresses the oncogenic AKT, and mTOR mediates the oncogenic effects of AKT. YT and NK92 cells derived from NK cell lymphomas were used. miR-494-3p inhibited PTEN with secondary activation of AKT in NK92 cells, and miR-142-3p inhibited RICTOR, a key component of the mTOR complex, with secondary suppression of AKT in YT cells. Significantly, T-bet inhibited the PTEN-AKT-mTOR/RICTOR pathway through induction of PTEN and suppression of RICTOR. Therefore, a molecular circuit of T-bet, PTEN, AKT, and RICTOR is regulated by miR-BART20-5p, miR-494-3p, and miR-142-3p. This circuit is involved in the pathogenesis of NNL. Hence, antagomirs to miR-BART20-5p or miR-494-3p, miR-142-3p mimics, or AKT inhibitors may be useful in NNL therapy.

The CTNNB1 gene encode the β-catenin protein which is a core unit of the cadherin/catenin multiprotein complex. The loss-of-function mutation of the CTNNB1 gene recently has been confirmed as a cause of intellectual disability. Previous studies have found that patients with CTNNB1 gene mutation may have other clinical manifestation such as microcephaly, abnormal facial features, motor and language delays, and mild visual defects. Here, we reported a 27-year-old Chinese pregnant woman with a severe intellectual disability and serious visual defects who was detected with a novel splice mutation (c.734+1G>A) in CTNNB1 gene by whole-exome sequencing and confirmed by Sanger sequencing. Further investigation showed that the variant was inherited from her mother with similar phenotypes. This report not only helps to expand the mutant spectrum of the CTNNB1 gene but also prompts a new insight into genetic diagnosis in patients with both serious intellectual disability and visual defects. Electronic supplementary material The online version of this article (10.1007/s10072-019-03823-5) contains supplementary material, which is available to authorized users.

New Findings What is the central question of this study?This study was designed to investigate the molecular mechanism and biological roles of long non‐coding RNA activated by transforming growth factor‐β (lncRNA ATB) in the progression of cervical cancer. What is the main finding and its importance?Our study provided new insight into the cross‐talk between lncRNA ATB, miR‐144 and ITGA6, shedding light on the therapy for cervical cancer. Abstract The present study was designed to investigate the molecular mechanism and biological roles of long non‐coding RNA activated by transforming growth factor‐β (lncRNA ATB) in the progression of cervical cancer. The expression levels of lncRNA ATB, miR‐144 and integrin α6 (ITGA6) were detected in human cervical cancer cell lines using quantitative real‐time PCR and western blotting. Cell viability was quantified by MTT assay at 12, 24, 36, 48 and 72 h after transfection, and cell invasion was determined by the Transwell migration assay. The association among lncRNA ATB, miR‐144 and ITGA6 was disclosed by a dual‐luciferase reporter assay. We found that lncRNA ATB was highly expressed in human cervical cancer cell lines. Further investigation indicated that lncRNA ATB functioned as a competitive endogenous RNA (ceRNA) for miR‐144 to promote cervical cancer cell proliferation and invasion. We demonstrated that ITGA6 was a direct target of miR‐144, and lncRNA ATB facilitated the proliferation and invasion of cervical cancer cells via the miR‐144/ITGA5 axis. In conclusion, the lncRNA ATB/miR‐144/ITGA6 axis might be a promising therapeutic target for cervical cancer.