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Myofibroblasts characterized by alpha smooth muscle actin(alpha-SMA) expression play a key role in pulmonary fibrosis. Transforming growth factor-beta1 (TGF-beta1) is likely to be involved in the emergence of myofibroblasts, but the intracellular signal pathways for this process have not been well determined. The aim of the present study was to investigate the role of mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling pathways in TGF-beta1-induced alpha-SMA expression in human fetal lung fibroblasts (HLF-02). We found that TGF-beta1 treatment activated p38 kinase and extracellular signal-regulated kinase (Erk) in HLF-02 cells. The induction of alpha-SMA by TGF-beta1 was suppressed by p38 kinase inhibitor (SB203580) and Erk inhibitor (PD98059). AP-1 inhibitor curcumin also inhibited TGF-beta1-induced alpha-SMA expression. In addition, dominant negative mutant c-Jun (TAM67) downregulated TGF-beta1-induced AP-1 transactivation and alpha-SMA expression. In additional, PD98059 but not SB203580 inhibited the AP-1 DNA binding activity induced by TGF-beta1. Based on these findings, we conclude that p38 kinase, Erk, and AP-1 are responsible for the alpha-SMA expression induced by TGF-beta1 in human fetal lung fibroblasts. Erk is involved in inducing alpha-SMA expression via AP-1 activation.

Our objective was to investigate the expression of HMGA1 mRNA and protein in hepatocellular carcinoma (HCC) and the correlation between its expression and clinical pathological characteristics and prognosis. HMGA1 expression was determined at both the mRNA level and the protein level in 30 HCC tissues and their corresponding paracancer liver tissues (PCLTs) and 2 normal liver tissues by RT-PCR and IHC. Follow-up study was done on the 30 patients involved in this research. HMGA1 mRNA was detected in nine cases of HCC tissues and two PCLTs, for a positivity rate of 30% and 6.7%, respectively (P < 0.05), whereas no HMGA1 mRNA expression was found in normal liver tissues. Clinicopathological analysis revealed that HMGA1 mRNA expression was significantly correlated with Edmondson's grade (P < 0.05). HMGA1 protein was detected in four HCC tissues by IHC and located mainly in the nuclei; no positive staining was found in PCLTs. Follow-up study showed that HMGA1 mRNA-positive patients had a higher risk of recurrence/metastasis and a shorter survival than negative cases (P < 0.05). Our findings indicate that HMGA1 may be involved in the carcinogenesis and invasiveness of HCC and the determination of HMGA1 can be of great value in predicting the prognosis of patients with HCC.

Radioresistance has been one of the impediments to effective nasopharyngeal carcinoma (NPC) therapy in clinical settings. Epstein‐Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is expressed in NPC and has potent effects on radioresistance. It has been detected in extracellular vesicles (EVs) or exosomes and shown to promote tumor proliferation and invasive potential. However, whether LMP1‐positive EVs can confer radioresistance to cancer cells and the mechanism used to promote radioresistance need to be elucidated. In this study, the data showed that EVs derived from LMP1‐positive NPC cells could induce recipient NPC cell proliferation and invasion and suppress apoptosis, especially promoting radioresistance. In addition, LMP1 could increase the secretion of LMP1‐positive EVs. Furthermore, transmitted LMP1 subsequently performed its oncogenic functions through activating P38 MAPK signaling in recipient cells, and inhibiting P38 activity could efficaciously restore the sensitivity of NPC cells to ionizing radiation (IR). Finally, we found that LMP1‐positive EVs could promote tumor growth and P38 inhibition eliminates this promoting effect in vivo, and EV formation is associated with a poor prognosis in NPC patients. These results showed that a few cells expressing LMP1 could enhance the radioresistance of NPC cells through potentially impacting the infected host and also modulating the tumor microenvironment.