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The role of sequence complexity in 23 051 somatic missense mutations including 73 well-known mutation hotspots across 22 major cancers was studied in human TP53 proteins. A role for sequence complexity in TP53 protein mutations is suggested since (i) the mutation rate significantly increases in low amino acid pair bias complexity; (ii) probability distribution complexity increases following single point substitution mutations and strikingly increases after mutation at the mutation hotspots including six detectable hotspot mutations (R175, G245, R248, R249, R273, and R282); and (iii) the degree of increase in distribution complexity is significantly correlated with the frequency of missense mutations (r = −0.5758, P < 0.0001) across 20 major types of solid tumors. These results are consistent with the hypothesis that amino acid pair bias and distribution probability may be used as novel measures for protein sequence complexity, and the degree of complexity is related to its susceptibility to mutation, as such, it may be used as a predictor for modeling protein mutations in human cancers. [ABSTRACT FROM AUTHOR]

As a famous acupuncturist in the world, professor ZHANG Jin believes the key of acupuncture technique is the use of force, and the understanding of the "concentrating the force into needle body" is essential to understand the essence of acupuncture technique. With deep study of Huangdi Neijing ( The Inner Canon of Huangdi ) and Zhenjiu Dacheng ( Compendium of Acupuncture and Moxibustion ), the author further learned professor ZHANG Jin 's theory and operation specification of "concentrating force into needle body, so the force arriving before and together with needle". The whole-body force should be subtly focused on the tip of needle, and gentle force at tip of needle could get significant reinforcing and reducing effect. In addition, proper timing at tip of needle could start reinforcing and reducing effect, lead qi to disease location, and achieve superior clinical efficacy.

Background: Overexpression of Metastasis-associated protein 1 (MTA1) in various cancer cells promotes tumor invasion and migration and predicts cancer patients' poor prognosis. The pilot RNA-Seq data from our laboratory indicated that Epithelial cell adhesion molecule (EpCAM) was statistically reduced in MTA1-silencing cells. EpCAM has been recognized as more than a mere cell adhesion molecule and recent findings have revealed its causal role in mediating migratory and invasive capacity. Thus, this study was aimed to explore whether MTA1 was able to upregulate EpCAM expression and, consequently, modulate its effects on invasion and migration of the lung cancer cells as well as patients' prognosis., Methods: We checked the EpCAM expression by overexpressing or silencing MTA1 in lung cancer cells. Furthermore, these lung cancer cells with stably overexpressed or silenced MTA1 were transfected with siEpCAM or EpCAM-expressing plasmids and then subjected to western blot, invasion and migration assays. In addition, patients (n = 118) with early-stage lung cancer were enrolled in this study to confirm the correlations between MTA1 and EpCAM and pathoclinical parameters by using immunohistochemistry (IHC). All statistical analyses were performed with SPSS 20.0 statistical software., Results: MTA1 upregulated EpCAM expression in lung cancer cell lines, and EpCAM overexpression rescued the inhibitory effects by silencing MTA1 on cell invasion and migration in vitro. What's more, both MTA1 and EpCAM, correlated to each other, were overexpressed in lung cancer tissues and significantly correlated with their clinical stages, tumor diameters, lymph node metastasis. Multivariate analysis indicated that local advancement (p = 0.03), MTA1 overexpression (p = 0.001) and EpCAM overexpression (p = 0.045) of the lung cancer tissues remained significant in predicting unfavorable overall survival., Conclusions: We revealed a new molecular mechanism of MTA1-mediated invasion and metastasis in lung cancer through downstream target EpCAM, and interfering with EpCAM function may be a novel therapeutic strategy for treatment of MTA1-overexpressing lung carcinoma.

As a component of the nuclear remodeling and deacetylation complex (NuRD complex), metastasis-associated gene 1 (MTA1) has been reported to play a key role in cancer malignancy. However, whether MTA1 functions in small cell lung cancer (SCLC) malignant behavior and whether it is feasible to be used as a therapeutic target have not been evaluated. The present study aimed to investigate the effects of MTA1 downregulation on SCLC malignancy. First we demonstrated the overexpression of MTA1 in SCLC specimens. After knocking down the MTA1 level by specific siRNA sequence, the biological consequences on proliferation, migration, invasion and apoptosis were evaluated. The results showed that MTA1 silencing had potent suppressive effects on SCLC proliferation, migration and invasion. Apoptosis but not cell cycle arrest was induced in the MTA1-silenced SCLC cells. In summary, MTA1 plays a critical role in regulating the malignant behaviors of SCLC. Depleting MTA1 level may be an effective strategy by which to suppress SCLC growth and metastasis in future biotherapeutic attempts.