Circular RNAs (circRNAs) have confirmed to participate in diverse biological functions in cancer. However, the expression patterns of circRNAs on hepatocellular carcinoma (HCC) remains unclear. In the present study, we clarified that hsa_circRNA_104348 was dramatically upregulated in HCC tissues and cells. Patients with HCC displaying high hsa_circRNA_104348 level possessed poor prognosis. Has_circ_104348 facilitated proliferation, migration, and invasion, meanwhile suppressed apoptosis of HCC cell. Furthermore, hsa_circRNA_104348 directly targeted miR-187–3p, could regulate miR-187-3p to affect proliferation, migration, invasion, and apoptosis of HCC cells, and may have effect on Wnt/β-catenin signaling pathway. Moreover, RTKN2 could be a direct target of miR-187-3p. In addition, knockdown of hsa_circRNA_104348 attenuated HCC tumorigenesis and lung metastasis in vivo. Taken together, these findings indicated that circular RNA hsa_circRNA_104348 might function as a competing endogenous RNA (ceRNA) to promotes HCC progression by targeting miR-187–3p/RTKN2 axis and activating Wnt/β-catenin pathway.

Liver fibrosis and hepatocellular carcinoma (HCC) have worldwide impact but continue to lack safe, low cost and effective treatments. In this study, we show how the simple polyamine spermidine can relieve cancer cell defects in autophagy which trigger oxidative stress-induced cell death and promote liver fibrosis and HCC. We found that the autophagic marker protein LC3 interacted with the microtubule-associated protein MAP1S which positively regulated autophagy flux in cells. MAP1S stability was regulated in turn by its interaction with the histone deacetylase HDAC4. Notably, MAP1S-deficient mice exhibited a 20% reduction in median survival and developed severe liver fibrosis and HCC under stress. Wild-type mice or cells treated with spermidine exhibited a relative increase in MAP1S stability and autophagy signaling via depletion of cytosolic HDAC4. Extending recent evidence that orally administered spermidine can extend lifespan in mice, we determined that life extension of up to 25% can be produced by lifelong administration which also reduced liver fibrosis and HCC foci as induced by chemical insults. Genetic investigations established that these observed impacts of oral spermidine administration relied upon MAP1S-mediated autophagy. Our findings offer a preclinical proof of concept for the administration of oral spermidine to prevent liver fibrosis and HCC and potentially extend lifespan.

With increases in the mortality rate and number of patients with prostate cancer (PCa), PCa, particularly the advanced and metastatic disease, has been the focus of a number of studies globally. Over the past seven decades, androgen deprivation therapy has been the primary therapeutic option for patients with advanced PCa; however, the majority of patients developed a poor prognosis stage of castration resistant prostate cancer (CRPC), which eventually led to mortality. Due to CRPC being incurable, laboratory investigations and clinical studies focusing on CRPC have been conducted worldwide. Clarification of the molecular pathways that may lead to CRPC is important for discovering novel therapeutic strategies to delay or reverse the progression of disease. A sustained androgen receptor (AR) signal is still regarded as the main cause of CRPC. Increasing number of studies have proposed different potential mechanisms that cause CRPC, and this has led to the development of novel agents targeting the AR-dependent pathway or AR-independent signaling. In the present review, the major underlying mechanisms causing CRPC, including several major categories of AR-dependent mechanisms, AR bypass signaling, AR-independent mechanisms and other important hypotheses (including the functions of autophagy, PCa stem cell and microRNAs in CRPC progression), are summarized with retrospective pre-clinical or clinical trials to guide future research and therapy.