Yanxia Liu

A C. elegans neurosecretory signaling system regulates whether animals enter the reproductive life cycle or arrest development at the long-lived dauer diapause stage. daf-2, a key gene in the genetic pathway that mediates this endocrine signaling, encodes an insulin receptor family member. Decreases in DAF-2 signaling induce metabolic and developmental changes, as in mammalian metabolic control by the insulin receptor. Decreased DAF-2 signaling also causes an increase in life-span. Life-span regulation by insulin-like metabolic control is analogous to mammalian longevity enhancement induced by caloric restriction, suggesting a general link between metabolism, diapause, and longevity.

We show here that the lin-11 LIM homeobox gene is expressed in nine classes of head, ventral cord, and tail neurons and functions at a late step in the development of a subset of these neurons. In a lin-11 null mutant, all lin-11-expressing neurons are generated. Several of these neurons, however, exhibit neuroanatomical as well as functional defects. In the lateral head ganglion, lin-11 functions in a neural network that regulates thermosensory behavior. It is expressed in the AIZ interneuron that processes high temperature input and is required for the function of AIZ in the thermoregulatory neural network. Another LIM homeobox gene, ttx-3, functions in the antagonistic thermoregulatory interneuron AIY (). Thus, distinct LIM genes specify the functions of functionally related antagonistic interneurons within a neural network dedicated for thermoregulatory processes. Both ttx-3 and lin-11 expression are maintained throughout adulthood, suggesting that these LIM homeobox genes play a role in the functional maintenance of this neural circuit. We propose that particular LIM homeobox genes specify the distinct features of functionally related neurons that generate patterned behaviors.

Krüppel-like transcription factor (KLF) family is involved in tumorigenesis in different types of cancer. However, the importance of KLF family in gastric cancer is unclear. Here, we examined KLF gene expression in five paired liver metastases and primary gastric cancer tissues by RT-PCR, and immunohistochemistry was used to study KLF8 expression in 206 gastric cancer samples. The impact of KLF8 expression on glycolysis, an altered energy metabolism that characterizes cancer cells, was evaluated. KLF8 showed the highest up-regulation in liver metastases compared with primary tumours among all KLF members. Higher KLF8 expression associated with larger tumour size (P < 0.001), advanced T stage (P = 0.003) and N stage (P < 0.001). High KLF8 expression implied shorter survival outcome in both TCGA and validation cohort (P < 0.05). Silencing KLF8 expression impaired the glycolysis rate of gastric cancer cells in vitro. Moreover, high KLF8 expression positively associated with SUVmax in patient samples. KLF8 activated the GLUT4 promoter activity in a dose-dependent manner (P < 0.05). Importantly, KLF8 and GLUT4 showed consistent expression patterns in gastric cancer tissues. These findings suggest that KLF8 modulates glycolysis by targeting GLUT4 and could serve as a novel biomarker for survival and potential therapeutic target in gastric cancer.

High mobility group proteins (HMGs) are the second most abundant chromatin proteins and exert global genomic functions in the establishment of active or inactive chromatin domains. Through interaction with nucleosomes, transcription factors, nucleosome-remodeling machines and histones, the HMGs family proteins contribute to the fine tuning of transcription in response to rapid environmental changes. Mammalian high mobility group Bs (HMGBs) are characterized by two tandem HMG box domains followed by a long acidic tail. Recent studies demonstrated that high expression of HMGBs has been found in many cancers, such as prostate, kidney, ovarian, and gastric cancers. However, their roles in pancreatic cancer have seldom been reported. In this study, we assessed the diagnostic and prognostic values of HMGBs proteins, including HMGB1, HMGB2, and HMGB3, in pancreatic cancer from the Cancer Genome Atlas (TCGA) dataset. Our results demonstrated that HMGB2 predicted poor prognosis in pancreatic cancer. In vitro studies demonstrated that silencing HMGB2 inhibited cell proliferation and viability. Mechanistically, our results demonstrated that silencing HMGB2 decreased hypoxia inducible factor 1α (HIF1α) protein level and inhibited HIF1α-mediated glycolysis process. Further analysis indicated that HIF1α-targeted glycolytic genes, including GLUT1, HK2, and LDHA, are all prognostic factors and positively correlated with HMGB2 expression. Taken together, we discovered new prognostic and predictive markers for pancreatic cancer, and shed light on the novel function of HMGB2 in glycolytic control in cancer.