HIF-1α, one of the most extensively studied oncogenes, is activated by a variety of microenvironmental factors. The resulting biological effects are thought to depend on its transcriptional activity. The RNAse enzyme Dicer is frequently downregulated in human cancers, which has been functionally linked to enhanced metastatic properties; however, current knowledge of the upstream mechanisms regulating Dicer is limited. In the present study, we identified Dicer as a HIF-1α–interacting protein in multiple types of cancer cell lines and different human tumors. HIF-1α downregulated Dicer expression by facilitating its ubiquitination by the E3 ligase Parkin, thereby enhancing autophagy-mediated degradation of Dicer, which further suppressed the maturation of known tumor suppressors, such as the microRNA let-7 and microRNA-200b. Consequently, expression of HIF-1α facilitated epithelial-mesenchymal transition (EMT) and metastasis in tumor-bearing mice. Thus, this study uncovered a connection between oncogenic HIF-1α and the tumor-suppressive Dicer. This function of HIF-1α is transcription independent and occurs through previously unrecognized protein interaction–mediated ubiquitination and autophagic proteolysis.

A lipid emulsion composed of soybean oil (long-chain triglycerides, LCT), medium-chain triglycerides (MCT) and n-3 poly-unsaturated fatty acids (PUFAs) was evaluated for immune-modulation efficacy, safety, and tolerance in patients undergoing major surgery for gastric and colorectal cancer.

This study investigated the clinicopathologic characteristics and survival of women diagnosed with pregnancy-associated breast cancer (PABC) in Taiwan. PABC is defined as breast cancer diagnosed during pregnancy or within 1 year after obstetric delivery. Our sample of PABC patients (N = 26) included all patients diagnosed at a major medical center in northern Taiwan from 1984 through 2009. Among these patients, 15 were diagnosed during pregnancy and 11 were diagnosed within 1 year after delivery. The comparison group included 104 patients within the same age range as the PABC patients and diagnosed with breast cancer not associated with pregnancy from 2004 through 2009 at the same hospital. Patients' initiating treatment delayed, 5-year and 10-year overall survival were delineated by stratified Kaplan-Meier estimates. Patients' characteristics were associated with initiating treatment delayed was evaluated with multivariate proportional hazards modeling. Antepartum PABC patients were younger and had longer time between diagnosis and treatment initiation than postpartum PABC patients. The predictor of treatment delayed was including birth parity, cancer stage, and pregnancy. The PABC group had larger tumors, more advanced cancer stage, and tumors with less progesterone receptor than the comparison group. The antepartum PABC patients had higher mortality than postpartum PABC and comparison groups within 5 years after diagnosis. Based on these results, we confirmed that pregnant women with breast cancer were more likely to delay treatment. Therefore, we recommend that breast cancer screening should be integrated into the prenatal and postnatal routine visits for early detection of the women's breast problems.

TAR (HIV-1) RNA binding protein 2 (TARBP2) is an RNA-binding protein participating in cytoplasmic microRNA processing. Emerging evidence has shown the oncogenic role of TARBP2 in promoting cancer progression, making it an unfavorable prognosis marker for breast cancer. Hypoxia is a hallmark of the tumor microenvironment which induces hypoxia-inducible factor-1α (HIF-1α) for transcriptional regulation. HIF-1α is prone to be rapidly destabilized by the ubiquitination–proteasomal degradation system. In this study, we found that TARBP2 expression is significantly correlated with induced hypoxia signatures in human breast cancer tissues. At a cellular level, HIF-1α protein level was maintained by TARBP2 under either normoxia or hypoxia. Mechanistically, TARBP2 enhanced HIF-1α protein stability through preventing its proteasomal degradation. In addition, downregulation of multiple E3 ligases targeting HIF-1α (VHL, FBXW7, TRAF6) and reduced ubiquitination of HIF-1α were also induced by TARBP2. In support of our clinical findings that TARBP2 is correlated with tumor hypoxia, our IHC staining showed the positive correlation between HIF-1α and TARBP2 in human breast cancer tissues. Taken together, this study indicates the regulatory role of TARBP2 in the ubiquitination–proteasomal degradation of HIF-1α protein in breast cancer.