MicroRNA (miR)-355 Suppressed Small Cell Lung Cancer Cell Metastasis via Regulating P38 Mitogen-Activated Protein Kinases (MAPKs) Signaling

MicroRNA (miR)-355 was reported to mediate p38 mitogen-activated protein kinases (MAPKs) signaling, which exerted an effect on cell invasion and metastasis. But whether miR-355 could inhibit small cell lung cancer cell line H446 cell metastasis by regulating p38 MAPKs signaling needs further study. H446 cells were cultured to establish miR-355 overexpression group and blank group. The expression of MT1-MMP, the activity and migration of H446 cells were evaluated. Further, the ability of invasion, the level of p-p38 MAPKs and the activity degree of MT1-MMP were observed in H446 cells. MT1-MMP was mainly expressed on the cell membrane. miR-355 overexpression significantly decreased cellular viability and reduced MT1-MMP and p-p38 MAPKs levels relative to the blank group without influencing p38 MAPKs level. In addition, miR-355 overexpression suppressed cell migration and invasive ability in H446 cells. Finally, miR-355 overexpression reduced pro-MMP and MMP-2 activity in H446 cells. miR-355 overexpression suppressed H446 cell metastasis through regulating P38 MAPKs signaling.

A Review: Mechanism of Phyllanthus urinaria in Cancers—NF-κB, P13K/AKT, and MAPKs Signaling Activation

Phyllanthus urinaria has been characterized for its several biological and medicinal effects such as antiviral, antibacterial, anti-inflammatory, anticancer, and immunoregulation. In recent years, Phyllanthus urinaria has demonstrated potential to modulate the activation of critical pathways such as NF-κB, P13K/AKT, and ERK/JNK/P38/MAPKs associated with cell growth, proliferation, metastasis, and apoptotic cell death. To date, there is much evidence indicating that modulation of cellular signaling pathways is a promising approach to consider in drug development and discovery. Thus, therapies that can regulate cancer-related pathways are longed-for in anticancer drug discovery. This review’s focus is to provide comprehensive knowledge on the anticancer mechanisms of Phyllanthus urinaria through the regulation of NF-κB, P13K/AKT, and ERK/JNK/P38/MAPKs signaling pathways. Thus, the review summarizes both in vitro and in vivo effects of Phyllanthus urinaria extracts or bioactive constituents with emphasis on tumor cell apoptosis. The literature information was obtained from publications on Google Scholar, PubMed, Web of Science, and EBSCOhost. The key words used in the search were “Phyllanthus” or “Phyllanthus urinaria” and cancer. P. urinaria inhibits cancer cell proliferation via inhibition of NF-κB, P13K/AKT, and MAPKs (ERK, JNK, P38) pathways to induce apoptosis and prevents angiogenesis. It is expected that understanding these fundamental mechanisms may help stimulate additional research to exploit Phyllanthus urinaria and other natural products for the development of novel anticancer therapies in the future.

p38-MAPK-mediated translation regulation during early blastocyst development is required for primitive endoderm differentiation in mice

Successful specification of the two mouse blastocyst inner cell mass (ICM) lineages (the primitive endoderm (PrE) and epiblast) is a prerequisite for continued development and requires active fibroblast growth factor 4 (FGF4) signaling. Previously, we identified a role for p38 mitogen-activated protein kinases (p38-MAPKs) during PrE differentiation, but the underlying mechanisms have remained unresolved. Here, we report an early blastocyst window of p38-MAPK activity that is required to regulate ribosome-related gene expression, rRNA precursor processing, polysome formation and protein translation. We show that p38-MAPK inhibition-induced PrE phenotypes can be partially rescued by activating the translational regulator mTOR. However, similar PrE phenotypes associated with extracellular signal-regulated kinase (ERK) pathway inhibition targeting active FGF4 signaling are not affected by mTOR activation. These data indicate a specific role for p38-MAPKs in providing a permissive translational environment during mouse blastocyst PrE differentiation that is distinct from classically reported FGF4-based mechanisms.

Correction to: Total saponin from Anemone flaccida Fr. Schmidt abrogates osteoclast differentiation and bone resorption via the inhibition of RANKL-induced NF-κB, JNK and p38 MAPKs activation

An amendment to this paper has been published and can be accessed via the original article.

Development of a Lung Cancer Model in Wistar Rat and In Silico Screening of its Biomarkers.

Background: Cancer is caused by three factors: Nutrition, inflammation and cigarette smoke. This study in rat experimental models would enable us to understand the mechanism of lung cancer caused by NNK to which humans are continuously exposed, help us understand possible molecular targets, design drugs for humans against lung cancer. Aim: A lung cancer model was developed by administering tobacco specific carcinogen: NNK [4-methylnitrosamino)-1-(3-pyridyl)-1-butanone] to male wistar rats in 24 weeks. Further, In silico approach was followed to screen the molecular targets. Methods: A method was established in which subcutaneous and intraperitoneal injections of NNK were administered to male wistar rats simultaneously. For authentication of lung cancer in vivo we performed molecular docking simulations with protein biomarkers:Cox-2, p53, p38 MAPKs and EGFR using Hex-Discovery Studio, Schrödinger-maestro software. Results: Lung morphology and histopathology indicated the initiation of bronchiolar epithelial hyperplasia, squamous dysplasia beginning in cancer 1 group after 16 weeks NNK exposure. 66.66% incidence of squamous cell carcinoma (SCC), 33.3% incidence of adenocarcinoma in cancer 2 group after being exposed to NNK. Results indicated that the SCC and adenocarcinoma gradually increased from 66.66% to 85.71% in cancer 2 group and 33.33% to 42.58% in cancer 3 groups respectively. Docking results indicate the total binding energy and glide energy of Cox-2, p53, p38 MAPKs, EGFR : 38.14, -211.58, -181.58, - 213.05 Kcal/mol and -39.25, -32.16,-36.49, -40.19 Kcal/mol, respectively. Conclusion: Pulmonary adenocarcinoma developed in 24 weeks, in silico experiments confirm EGFR to be the most potential target for NNK induced lung Cancer.