Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession.

PKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a "pseudokinase", contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PKM2 remain unclear. This study demonstrated that TRIB2, not a "pseudokinase", has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. The elevated pSer37-PKM2 would subsequently promote the PKM2 dimers to enter into nucleus and increase the expression of LDHA, GLUT1, and PTBP1. The aerobic glycolysis is then elevated to promote cancer cell proliferation and migration in TRIB2- or PKM2-overexpressed cultures. The glucose uptake and lactate production increased, but the ATP content decreased in TRIB2- or PKM2-treated cultures. Experiments of TRIB2-/- mice further supported that TRIB2 could regulate aerobic glycolysis by PKM2. Thus, these results reveal the new kinase activity of TRIB2 and its mechanism in cancer metabolism may be related to regulating PKM2 to promote lung cancer cell proliferation in vitro and in vivo, suggesting promising therapeutic targets for cancer therapy by controlling cancer metabolism.

[Advance on pharmacokinetics study of traditional Chinese medicine injections in recent ten years].

Traditional Chinese medicine(TCM) injections boast a definite efficacy and have been widely used in clinic. However, the problems in medication safety have been attracted increasing attention. Pharmacokinetics is of significance to guiding TCM injection administration regimen design and improving safety and effectiveness in clinical use. In recent years, with the improvement of ideas, technology and methods of TCM studies, the pharmacokinetic studies of TCM injections have been broadly performed, with a notable progress. This paper reviewed the advance in pharmacokinetics studies of TCM injections in recent ten years, which mainly focused on pre-clinical concentration-time course, distribution, metabolism and excretion in vivo based on analysis techniques, pharmacokinetic interactions of constitutes, impact of pathological state, pharmacokinetic interactions between TCM injection and chemical drugs, and clinical pharmacokinetics studies of TCM injections, in the expectation of providing reference for studies on quality control, product development and rational clinical use of TCM injections.

MicroRNAs as Therapeutic Targets for Anticancer Drugs in Lung Cancer Therapy.

MicroRNAs (miRNAs) are short, non-coding RNA molecules that regulate gene expression by translational repression or deregulation of messenger RNAs. Accumulating evidence suggests that miRNAs play various roles in the development and progression of lung cancers. Although their precise roles in targeted cancer therapy are currently unclear, miRNAs have been shown to affect the sensitivity of tumors to anticancer drugs. A large number of recent studies have demonstrated that some anticancer drugs exerted antitumor activities by affecting the expression of miRNAs and their targeted genes. These studies have elucidated the specific biological mechanism of drugs in tumor suppression, which provides a new idea or basis for their clinical application. In this review, we summarized the therapeutic mechanisms of drugs in lung cancer therapy through their effects on miRNAs and their targeted genes, which highlights the roles of miRNAs as targets in lung cancer therapy.

Cisplatin decreases cyclin D2 expression via upregulating miR­93 to inhibit lung adenocarcinoma cell growth.

MicroRNAs (miRNAs/miRs) serve important roles in the chemotherapeutic effect of anticancer drugs. To investigate the roles of miRNAs in cisplatin­induced suppression of lung adenocarcinoma cell proliferation, A549 cells were treated with different concentrations of cisplatin. An MTT assay demonstrated that cisplatin inhibited A549 cell proliferation in a dose­dependent manner. Cisplatin induced cell apoptosis and inhibited cell migration by increasing the levels of miR­93, miR­26a and miR­26b. Furthermore, as an upstream factor, miR­93 was proposed to regulate cyclin D2 expression in miR­93­transfected A549 cells. Cisplatin also induced Bcl­2­associated X protein expression, and decreased that of Bcl­2 and c­Myc in lung adenocarcinoma cells. In vivo analysis further supported that cisplatin inhibited lung adenocarcinoma cell growth by regulating cyclin D2 and miR­93 expression. In conclusion, our findings demonstrated that cisplatin could effectively inhibit lung adenocarcinoma cell proliferation by decreasing cyclin D2 expression via miR­93.