LASTR is a novel prognostic biomarker and predicts response to cancer immunotherapy in gastric cancer.

Gastric cancer (GC), a malignant tumor of digestive tract, is characterized by a high death rate. Thus, it is of particular importance to clarify the mechanisms of GC and gain new molecular targets for the sake of preventing and treating GC. It was reported that long non-coding RNAs (IncRNAs) are prognostic factors to cancer. Ferroptosis refers to a process of programmed cell death dependent on iron. This study sets out to investigate the expression and function of ferroptosis-related lncRNA (FRlncRNA) in GC. TCGA datasets offered RNA-seq data for 375 GC patients and clinical data for 443 GC patients. Based on Pearson's correlation analysis, we studied their expression and identified the FRlncRNAs. Differentially expressed prognosis related to FRlncRNA were determined with the help of the Wilcoxon test and univariate Cox regression analysis. To evaluate the accuracy of the prognostic capacity, researchers used the Kaplan-Meier technique, as well as univariate and multivariate Cox regression and receiver operating characteristic (ROC) curve studies. We also carried out the real-time PCR and CCK8 assays to examine the expression and function of FRlncRNA. In this study, we identified 50 ferroptosis-related DEGs which were involved in tumor progression. In addition, we identified 33 survival-related FRlncRNAs. Among them, lncRNA associated with SART3 regulation of splicing(LASTR) was confirmed to be highly expressed in GC specimens compared to non-tumor specimens in this cohort. Survival assays illuminated that the high LASTR expression predicted a shorter overall survival and progression-free survival of GC patients. Based on multivariate Cox regression analyses, it was confirmed that the GC had a worse chance of surviving the disease overall if their tumors expressed LASTR, which was an independent prognostic indication. Then, Loss-of-function tests showed that knocking down LASTR had a significant effect on reducing the proliferation of GC cells. Finally, we found that the expression of LASTR was negatively associated with CD8 T cells, T cells, Th17 cells, and T helper cells. Overall, our findings identified a novel survival-related FRlncRNA, LASTR which possibly can serve as a novel prognostic biomarker predicting response to cancer immunotherapy and therapeutic target for GC patients.

Prenatal inflammation exposure-programmed hypertension exhibits multi-generational inheritance via disrupting DNA methylome.

The multi-generation heredity trait of hypertension in human has been reported, but the molecular mechanisms underlying multi-generational inheritance of hypertension remain obscure. Recent evidence shows that prenatal inflammatory exposure (PIE) results in increased incidence of cardiovascular diseases, including hypertension. In this study we investigated whether and how PIE contributed to multi-generational inheritance of hypertension in rats. PIE was induced in pregnant rats by intraperitoneal injection of LPS or Poly (I:C) either once on gestational day 10.5 (transient stimulation, T) or three times on gestational day 8.5, 10.5, and 12.5 (persistent stimulation, P). Male offspring was chosen to study the paternal inheritance. We showed that PIE, irrespectively induced by LPS or Poly (I:C) stimulation during pregnancy, resulted in multi-generational inheritance of significantly increased blood pressure in rat descendants, and that prenatal LPS exposure led to vascular remodeling and vasoconstrictor dysfunction in both thoracic aorta and superior mesenteric artery of adult F2 offspring. Furthermore, we revealed that PIE resulted in global alteration of DNA methylome in thoracic aorta of F2 offspring. Specifically, PIE led to the DNA hypomethylation of G beta gamma (Gßγ) signaling genes in both the F1 sperm and the F2 thoracic aorta, and activation of PI3K/Akt signaling was implicated in the pathologic changes and dysregulated vascular tone of aortic tissue in F2 LPS-P offspring. Our data demonstrate that PIE reprogrammed DNA methylome of cells from the germline/mature gametes contributes to the development of hypertension in F2 PIE offspring. This study broadens the current knowledge regarding the multi-generation effect of the cumulative early life environmental factors on the development of hypertension.

[Effect of nesprin-1 in the differentiation of mouse embryonic stem cells into cardiomyocytes].

OBJECTIVE: To investigate the role of nesprin-1 in mouse embryonic stem cells differentiation into cardiomyocyte. METHODS: Hanging drop-suspension-adherence method was applied for the differentiation of mouse embryonic stem cells into cardiomyocytes under the inducing of salvia miltorrhiza and 5-azacytidine. Changes in nesprin-1 gene expression were detected by using Western blotting and immunofluorescent assay. RNA interference was used to reduce nesprin-1 protein levels to further investigate the importance of nesprin-1 in mouse embryonic stem cells differentiation, group I (target sequence AAAGCCAAGCACGCAACTA), group II (target sequence GGGAACCAACAGTGAGATT), group III (target sequence ACCAGGACATTGCGTACTA), and group IV (control group). RESULTS: The nesprin-1 isoform profile was altered in mouse embryonic stem cells differentiation. The rates of differentiation of the four groups were (17.78 +/- 1.92)%, (36.67 +/- 3.34)%, (44.42 +/- 5.08)%, (77.78 +/- 1.92)%; The rate of differentiation of group IV was higher than RNAi groups and the difference was significant (P < 0.05). In addition, compared with the control group, myosin in RNAi groups were dramatically reduced. CONCLUSION: Nesprin-1 played important roles in mouse embryonic stem cells differentiation into cardiomyocyte. Nesprin-1 isoforms might perform different functions in the process of mouse embryonic stem cells differentiation.