FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression / 医学前沿

FRMD6, a member of the 4.1 ezrin-radixin-moesin domain-containing protein family, has been reported to inhibit tumor progression in multiple cancers. Here, we demonstrate the involvement of FRMD6 in lung cancer progression. We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues. In addition, the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma (n = 75, P = 0.0054) and lung adenocarcinoma (n = 94, P = 0.0330). Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6. Mechanistically, FRMD6 interacts and colocalizes with mTOR and S6K, which are the key molecules of the mTOR signaling pathway. FRMD6 markedly enhances the interaction between mTOR and S6K, subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells. Furthermore, knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6-/- gene KO MEFs and mice. Altogether, our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.

Brain activities in patients with inflammatory bowel disease on resting-state functional MRI with amplitude of low-frequency fluctuation algorithm / 医学研究生学报

Objective Visceral pain in patients with inflammatory bowel disease (IBD) may be associated with the abnormal processing of pain in the central nervous system.The aim of the study is to investigate the characteristic changes of brain functions in the IBD patients using resting-state functional magnetic resonance imaging (rs-fMRI) with the amplitude of low-frequency fluctuation (ALFF) algorithm.Methods This study included 27 cases of IBD treated in our hospital from December 2015 to August of 2016 and 21 healthy volunteers as normal controls.We recorded the high-resolution structure imaging and rs-fMRI data, compared the brain activities of the two groups patients by ALFF analysis, and evaluated the correlation of the ALFF values with the clinical parameters of the IBD patients.Results Compared with the normal control group, the IBD patients showed significantly decreased ALFF values in the medial frontal gyrus, right putamen, right insula, left middle cingulate gyrus (MCC), and bilateral supplementary motor region (P<0.05), increased ALFF values in the middle frontal gyrus, left superior frontal gyrus, and medial prefrontal lobe region (P<0.05).The ALFF values in the inferior parietal lobule, precuneus and MCC of the IBD patients were correlated negatively with the blood sedimentation rate (r=-0.537,-0.588, and-0.588, P<0.05), disease course (P<0.05), and C-reactive protein (CRP) level (P<0.05), while that in the medial frontal gyrus positively with the CRP level (r=-0.623, P<0.001).Conclusion IBD patients have abnormal ALFF values in various brain regions, mainly in those involved in the processing of visceral pain and emotion.