Recent reports showed that haematological and neurological expressed 1-like (HN1L) gene participated in tumorigenesis and tumour invasion. However, the expression and role of HN1L in breast cancer remain to be investigated. Here, bioinformatics, western blot and immunohistochemistry were used to detect the expression of HN1L in breast cancer. Wound healing, transwell assay, immunofluorescence assay and mass spectrum were used to explore the role and mechanism of HN1L on the migration and invasion of breast cancer, which was confirmed in vivo using a nude mice model. Results showed that HN1L was significantly over-expressed in breast cancer tissues, which was positively correlated with M metastasis of breast cancer patients. Silencing HN1L significantly inhibited the invasion and metastasis of breast cancer cells in vitro and lung metastasis in nude mice metastasis model of breast cancer. Mechanistically, HN1L interacted with HSPA9 and affected the expression of HMGB1, playing a key role in promoting the invasion and metastasis of breast cancer cell. These results suggested that HN1L was an appealing drug target for breast cancer. 相似文献
The ADP-ribosylation factor-like proteins (ARLs) have been proved to regulate the malignant phenotypes of several cancers. However, the exact role of ARLs in gastric cancer (GC) remains elusive. In this study, we systematically investigate the expression status, interactive relations, potential pathways, genetic variations and clinical values of ARLs in GC. We find that ARLs are significantly dysregulated in GC and involved in various cancer-related pathways. Subsequently, machine learning models identify ARL4C as one of the two most significant clinical indicators among ARLs for GC. Furthermore, ARL4C silencing remarkably inhibits the growth and metastasis of GC cells both in vitro and in vivo. Moreover, enrichment analysis indicates that ARL4C is highly correlated with TGF-β1 signalling. Correspondingly, TGF-β1 treatment dramatically increases ARL4C expression and ARL4C knockdown inhibits the phosphorylation level of Smads, downstream factors of TGF-β1. Meanwhile, the coexpression of ARL4C and TGF-β1 worsens the prognosis of GC patients. Our work comprehensively demonstrates the crucial role of ARLs in the carcinogenesis of GC and the specific mechanisms underlying the GC-promoting effects of TGF-β1. More importantly, we uncover the great promise of ARL4C-targeted therapy in improving the efficacy of TGF-β1 inhibitors for GC patients. 相似文献
Hepatocellular carcinoma (HCC) is one of the most aggressive tumours with marked fibrosis. Mycophenolate mofetil (MMF) was well-established to have antitumour and anti-fibrotic properties. To overcome the poor bioavailability of MMF, this study constructed two MMF nanosystems, MMF-LA@DSPE-PEG and MMF-LA@PEG-PLA, by covalently conjugating linoleic acid (LA) to MMF and then loading the conjugate into polymer materials, PEG5k-PLA8k and DSPE- PEG2k, respectively. Hepatocellular carcinoma cell lines and C57BL/6 xenograft model were used to examine the anti-HCC efficacy of nanoparticles (NPs), whereas NIH-3T3 fibroblasts and highly-fibrotic HCC models were used to explore the anti-fibrotic efficacy. Administration of NPs dramatically inhibited the proliferation of HCC cells and fibroblasts in vitro. Animal experiments revealed that MMF-LA@DSPE-PEG achieved significantly higher anti-HCC efficacy than free MMF and MMF-LA@PEG-PLA both in C57BL/6 HCC model and highly-fibrotic HCC models. Immunohistochemistry further confirmed that MMF-LA@DSPE-PEG dramatically reduced cancer-associated fibroblast (CAF) density in tumours, as the expression levels of alpha-smooth muscle actin (α-SMA), fibroblast activation protein (FAP) and collagen IV were significantly downregulated. In addition, we found the presence of CAF strongly correlated with increased HCC recurrence risk after liver transplantation. MMF-LA@DSPE-PEG might act as a rational therapeutic strategy in treating HCC and preventing post-transplant HCC recurrence. 相似文献
Long non-coding RNA (lncRNA) represents a new direction to identify expression profiles and regulatory mechanisms in various organisms. Here, we report the first dataset of lncRNAs of the golden snub-nosed monkey (GSM), including 12,557 putative lncRNAs identified from seven organs. Compared with mRNA, GSM lncRNA had fewer exons and isoforms, and longer length. LncRNA showed more obvious tissue-specific expression than mRNA. However, for the top ten most abundant genes in each organ, mRNAs expression was more tissue-specific than lncRNAs. By identification of specifically expressed lncRNAs and mRNAs in each organ, it indicates that the expression of SEG-lncRNA (specifically expressed lncRNA) and SEG-mRNA (specifically expressed mRNA) had high correlation. In particular, combined our lncRNA and mRNA data, we identified 92 heart SEG-lncRNAs targeted ten mRNA genes in the oxidative phosphorylation pathway and upregulated the expression of these target genes such as ND4, ATP6, and ATP8. These may contribute to GSM adaption to its high-elevation environment. We also identified 171 liver SEG-lncRNAs, which targeted 27 genes associated with the metabolism of xenobiotics and leaded to high expression of these target genes in liver. These lncRNAs may play important roles in GSM adaptation to a folivory diet.
JAK/STAT plays an important role in cytokine signal transduction and it is potentially involved in the proinflammatory response during the early phase of severe acute pancreatitis (SAP). However, whether JAK2 activity is upregulated and whether JAK2 inhibition plays a role in the maintenance of pancreatic homeostasis during SAP is incompletely understood. Here we show that JAK2/STAT3 activity is highly elevated in SAP and blockade of JAK2 by AG-490 protects against SAP-induced pancreatic inflammation and injury. Gene expression and ELISA studies showed that JAK2 inhibition altered the cytokine profiles in both the circulation and pancreases. Further analysis revealed that JAK2 inhibition restored the level of cytokines critical for macrophage polarization towards M2 macrophage. Our findings suggest that pharmacological targeting at JAK2/STAT signalling may be an effective choice of therapeutic interventions against SAP. 相似文献