The human insulin-like growth factor-II (IGF-II) gene transcribes four mRNAs (P1 mRNA-P4 mRNA), and P3 mRNA overexpression contributes to hepatocarcinogenesis. IGF-II-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in P3 mRNA overexpression regulation and its role in hepatocellular carcinoma. Our results showed that miR-483-5p up-regulated P3 mRNA transcription by targeting the 5′-untranslated region (5′UTR) of P3 mRNA in hepatocellular carcinoma. The mechanism was involved in recruiting of an argonaute 1(Ago1)-argonaute 2 (Ago2) complex to the P3 mRNA 5′UTR and the P3 promoter of IGF-II gene by miR-483-5p, accompanied by increased enrichment of RNA polymerase II and activating histone marks histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 27 acetylation (H3K27ac), and histone 4 lysine 5/8/12/16 acetylation (H4Kac) at the P3 promoter. High miR-483-5p expression was an independent predictor for shorter survival of HCC patients. The findings suggest that miR-483-5p promotes P3 mRNA transcription by recruiting the Ago1-Ago2 complex to the P3 mRNA 5′UTR and is associated with poor prognosis of HCC. Our results display a potential new model for miRNAs to up-regulate gene expression.

Chronic liver diseases caused by various pathogenesis are marked by inflammatory infiltration and wound healing reaction, while their normal regeneration ability is impaired. The unbalance between the generation and the degradation of extracellular matrix (ECM) leads to collagen accumulation and develops into liver fibrosis. Inflammation, oxidative stress, and autophagy interact closely in the pathogenesis of hepatic fibrosis. Reactive Oxygen Species (ROS) can not only stimulate Kupffer cells to release massive inflammatory factors, but induce autophagy. However, the latter may suppress inflammatory reaction by inhibiting proinflammatory complex formation directly, and removing damaged organelles or pathogenic microorganism indirectly. At present, effective anti-fibrosis drugs are still lacking. Previous studies have found various natural compounds enabled liver protection through anti-inflammatory, antioxidant, and other mechanisms. In recent years, autophagy, a vital life activity, has been found to be involved in the mechanism of liver fibrosis. As a new target, developing anti-liver fibrosis drugs that regulate the activity of autophagy is very promising. In this review, we summarize the latest studies about natural compounds in the treatment of liver fibrosis by regulating autophagy.

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The present case study reported a rare case of duodenal metastasis from a lung adenocarcinoma. A 62-year-old male, who underwent radical lung cancer surgery two years ago, was readmitted to Guangzhou Red Cross Hospital complaining of epigastric pain. The esophagogastroduodenoscopy identified a 2.5x3.5 cm ulcerative lesion at the duodenum. Histopathological and immunohistochemical staining results confirmed that the lung adenocarcinoma had metastasized to the duodenum. The tumor cells were positive for cytokeratin-7, thyroid transcription factor-1 and napsin-A expression, but negative for caudal-related homeobox 2 expression. Prior to the second cycle of targeted treatment with anlotinib, the patient reported severe hematochezia. Therefore, an angiography and artery embolization were subsequently performed. However, the patient succumbed to acute kidney injury three days after the operation. The metastasis of lung cancer to the gastrointestinal tract is extremely rare and usually asymptomatic. However, when treating patients with lung cancer presenting with digestive symptoms or other distant metastatic sites, clinicians should consider the possibility of gastrointestinal metastasis so that it can be identified in a timely manner. If lesions exist, doctors should locate these and perform biopsies to conduct histopathological and immunohistochemical examinations to make a clear diagnosis.