Silencing of MicroRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells

Tamoxifen (TAM) and fulvestrant (FUL) represent the major adjuvant therapy to estrogen receptor-alpha positive (ER⁺) breast cancer patients. However, endocrine resistance to TAM and FUL is a great impediment for successful treatment. We hypothesized that miR-21 might alter the sensitivity of breast cancer cells to TAM or FUL by regulating cell autophagy. Using the ER⁺ breast cancer cells, we knockdown miR-21.by transfection with miR-21 inhibitor, then the cells were exposed to TAM or FUL and the percentages of apoptosis and autophagy were determined. Knockdown of miR-21 significantly increased the TAM or FUL-induced apoptosis in ER⁺ breast cancer cells. Further, silencing of miR-21 in MCF-7 cells enhanced cell autophagy at both basal and TAM or FUL-induced level. The increase of autophagy in miR-21-knockdown MCF-7 cells was also indicated by increase of beclin-1, LC3-II and increased GFP-LC3 dots. Importantly, knockdown of miR-21 contributed to autophagic cell death, which is responsible for part of TAM induced cell death in miR-21 inhibitor-transfected cells. Further analysis suggested that miR-21 inhibitor enhance autophagic cell death through inhibition of PI3K-AKT-mTOR pathway. MiR-21 coordinated the function of autophagy and apoptosis by targeting Phosphatase and tensin homolog (PTEN) through inhibition of PI3K-AKT-mTOR pathway. In conclusion, silencing of miR-21 increased the sensitivity of ER⁺ breast cancer cells to TAM or FUL by increasing autophagic cell death. Targeting autophagy-related miRNAs is a potential strategy for overcoming endocrine resistance to TAM and FUL.     

Seasonal influenza vaccination among cancer patients: A systematic review and meta-analysis of the determinants

Cancer patients are among high-risk individuals for whom seasonal influenza vaccine (SIV) is recommended, but rates of vaccination in this subpopulation remain suboptimal; even in jurisdictions with universal influenza vaccination programs. We sought to summarize the evidence to better understand the determinants of SIV uptake (vaccine receipt) among cancer patients. We searched MEDLINE, Embase, and CINAHL from 2000 to February 12, 2020, focusing on articles on the determinants of seasonal influenza vaccination among cancer patients, published in English. Study selection was conducted independently by 2 reviewers. One reviewer extracted data from the included studies and another reviewer checked the extracted data for errors. Outcomes were sociodemographic and health-related factors. We pooled adjusted results from studies using the inverse variance, random-effects method, and reported the odds ratios (OR) and their 95% confidence intervals (CI). Out of 2664 citations, 10 studies (mostly from USA and South Korea) met our eligibility criteria. Overall, being older (OR 2.23, 95% CI 1.46-3.38; I² 92.3%, [6 studies]), a nonsmoker (1.43, 1.32-1.51; I² 0%, [4 studies]), having a chronic illness (1.18, 1.07-1.29; I² 15.7%, [5 studies]), having had a medical check-up in the past year (1.75, 1.65-1.86; I² 0%, [2 studies]), and having health insurance (1.39, 1.13-1.72; I² 21.8%, [3 studies]) were associated with increased SIV uptake. Compared with being African-American, being Caucasian was also associated with increased SIV uptake (1.79, 1.47-2.13; I² 10.7%, [3 studies]). Limited evidence suggests seasonal influenza vaccination among cancer patients may be determined by some sociodemographic and health-related factors.     

SERPINA5 inhibits tumor cell migration by modulating the fibronectin–integrin β1 signaling pathway in hepatocellular carcinoma

In our previous study, we identified 1241 loci with somatic copy number alterations in human hepatocellular carcinoma (HCC) using Affymetrix SNP 6.0 arrays, and a putative cancer gene SERPINA5 was uncovered in a novel chromosomal region with recurrent copy number loss at 14q31.1–32.13. The SERPINA5 was reported to be deregulated in renal, breast, prostate and ovarian cancers. However, the roles of SERPINA5 in cancer remain greatly elusive. In this study, we found that the DNA dosage and expression level of the SERPINA5 gene were significantly decreased in HCC by quantitative real-time PCR. Notably, the expression levels of SERPINA5 negatively correlated with malignant progression of HCC. The SERPINA5 gene was further observed to reduce in vitro and in vivo metastatic potential of HCC cells. Moreover, secreted SERPINA5 protein also could inhibit the metastatic ability of HCC cells. Finally, we discovered that one of the mechanisms explaining SERPINA5 inhibition of HCC metastasis is through direct interaction with fibronectin and disruption of the fibronectin–integrin signaling pathway. These findings highlight an important role of SERPINA5 in the regulation of migratory and metastatic potentials of HCC and suggest a potential application of SERPINA5 in cancer treatment.