Myosins are a superfamily of actin-based molecular motor proteins, which hydrolyze ATP and generate various forms of eukaryotic motility and muscle contraction. Myosin light chain 20 (MLC20) is small ring around the neck region of heavy chain of myosins. Phosphorylation of MLC20 is thought to play a key role in regulation of smooth muscle contraction. Calcium- and calmodulin-dependent myosin light chain kinase (MLCK) is considered the primary regulator of MLC20 phosphorylation. However, several observations in smooth muscle contraction cannot be explained by the mode of phosphorylation. By performing a series of experiments in vitro and in vivo, we report here MLCK-independent MLC20 phosphorylation. Gene expression study reveals that expression of MLCK in smooth muscles is inconsistent with MLC20 phosphorylation at Ser19. None of inactivating calmodulin/MLCK, depriving of calcium and silencing MLCK expression by siRNA blocks effectively the phosphorylation of MLC20 at Ser19. In addition, by overexpressing active human MAP (mitogen-activated protein)-ERK kinase kinase-1 (MEKK1) and blocking its downstream messengers, we have demonstrated a new regulatory system of MLC phosphorylation via MEKK1, which downregulates Ser19 phosphorylation of MLC20 through its downstream molecules, p38, JNK, and ERK in human bladder smooth muscle cells.

Gastric cancer (GC) is the most common gastrointestinal cancer and the main cause of tumor-related death. Exploring markers for early diagnosis and new therapeutic targets is always on the way. In the last 10 years, long noncoding RNAs (lncRNAs) have been widely proved to be involved in the progress of many tumors and are regarded as potential targets for tumor therapy. We found that LINC00152, a newly identified lncRNA, was significantly upregulated in GC tissues and affected clinicopathological characteristics in GC patients. Furthermore, we observed that LINC00152 knockdown can significantly reduce cell proliferation and promote apoptosis in human gastric cancer cells. Further bioinformatic analysis indicated that LINC00152 competitively bound with miR-138 and regulated the expression of miR-138. Moreover, SIRT2 was further proved to be a downstream target of miR-138. Overall, this study elucidates the molecular mechanism of LINC00152 underlying the malignant phenotype of GC cells by mediating miR-138/SIRT2 axis, which provides a new understanding of the role and molecular mechanism of lncRNA in GC and also provides a new way for the treatment of gastric cancer.

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Background: Triple-negative breast cancer (TNBC) is a relatively rare subtype of breast cancer, and is prone to lymph node metastasis at early stage. However, there is a lack of prognosis prediction models. The purpose of this study is to develop and validate an effective nomogram for predicting the probability of lymph node metastasis in early-stage TNBC.Methods: We selected 26,775 eligible patients who were diagnosed with early-stage TNBC between 2010 and 2015 from the Surveillance, Epidemiology, and End Results database. All the patients were randomly divided into a training cohort and a validation cohort at a 7:3 ratio. The 266 patients in the validation cohort comprised from the Affiliated Jurong Hospital of Jiangsu University for medical records from January 2011 to August 2020 to identify patients with histologically confirmed early-stage TNBC. The predictive accuracy and identification capability of the nomogram of the clinical prediction model were determined using the concordance index (C-index), receiver operating characteristic curves (ROC), and calibration curves.Results: In all, 27,041 patients were included, with 18,929 patients in the training cohort and 8,112 patients in the validation cohort. Multivariate analysis of the training cohort showed the independent risk factors for lymph node metastasis were age, race, primary site, histological type, grade and tumor size, which were all included in the nomogram. In the training cohort, the nomogram presented robust discrimination, with a C-index of 0.712, which was similar to the C-index of 0.710 in the validation cohort. Consistently, the area under the ROC curve was 0.712 in the training cohort and 0.710 in the validation cohort, which both showed good predictive value for lymph node metastasis risk. The calibration curve showed a better agreement between the nomogram-predicted probability and the actual probability of lymph node metastasis risk.Conclusions: The prognostic nomogram for early-stage TNBC patients constructed here shows good application prospect and can assist clinicians in predicting lymph lode metastasis in early-stage TNBC.