Let-7a-5p inhibits triple-negative breast tumor growth and metastasis through GLUT12-mediated warburg effect
CANCER LETTERS
Authors: Shi, Yajiao; Zhang, Yanan; Ran, Fang; Liu, Jie; Lin, Jing; Hao, Xiaopeng; Ding, Lihua; Ye, Qinong
Abstract
Triple-negative breast cancer (TNBC) is known for its aggressive phenotype with limited treatment modalities and poor prognosis. The Warburg effect (aerobic glycolysis) is a hallmark of cancer that serves as a promising target for diagnosis and therapy. However, how aerobic glycolysis regulates TNBC remains largely unknown. Here, we show that the glucose transporter (GLUT) family member GLUT12 promotes TNBC tumor growth and metastasis in vitro and in vivo through regulating aerobic glycolysis. MicroRNA let-7a-5p, a tumor suppressor, inhibited GLUT12 expression by targeting its 3'-untranslated region, and suppressed GLUT12-mediated TNBC tumor growth, metastasis, and glycolytic function, including alterations of glucose uptake, lactate production, ATP generation, extracellular acidification rate, and oxygen consumption rate. Inhibiting aerobic glycolysis abolished the ability of let-7a-5p and GLUT12 to regulate TNBC cell proliferation, migration and invasion. In TNBC patients, GLUT12 was significantly upregulated, and let-7a-5p expression was inversely correlated with GLUT12 expression. High expression of let-7a-5p and GLUT12 predicted better and worse clinical outcomes, respectively. Taken together, our results indicate that the let-7a-5p/GLUT12 axis plays key roles in TNBC tumor growth and metastasis, and aerobic glycolysis, and is a potential target for TNBC treatment.
The state of enrollment on the National Health Insurance Scheme in rural Ghana after eight years of implementation
INTERNATIONAL JOURNAL FOR EQUITY IN HEALTH
Authors: Kwarteng, Anthony; Akazili, James; Welaga, Paul; Dalinjong, Philip Ayizem; Asante, Kwaku Poku; Sarpong, Doris; Arthur, Samuelina; Bangha, Martin; Goudge, Jane; Sankoh, Osman
Abstract
Background In 2004, Ghana implemented a national health insurance scheme (NHIS) as a step towards achieving universal health coverage. In this paper, we assessed the level of enrollment and factors associated with NHIS membership in two predominantly rural districts of northern Ghana after eight years of implementation, with focus on the poor and vulnerable populations. Methods A cross-sectional survey was conducted from July 2012 to December 2012 among 11,175 randomly sampled households with their heads as respondents. Information on NHIS status, category of membership and socio-demographic characteristics of household members was obtained using a structured questionnaire. Principal component analysis was used to compute wealth index from household assets as estimates of socio-economic status (SES). The factors associated with NHIS enrollment were assessed using logistic regression models. The reasons behind enrollment decisions of each household member were further investigated against their SES. Results Approximately half of the sampled population of 39,262 were registered with a valid NHIS card; 53.2% of these were through voluntary subscriptions by payment of premium whilst the remaining (46.8%) comprising of children below the ages of 18 years, elderly 70 years and above, pregnant women and formal sector workers were exempt from premium payment. Despite an exemption policy to ameliorate the poor and vulnerable households against catastrophic health care expenditures, only 0.5% of NHIS membership representing 1.2% of total exemptions granted on accounts of poverty and other social vulnerabilities was applied for the poor. Yet, cost of premium was the main barrier to NHIS registration (92.6%) and non-renewal (78.8%), with members of the lowest SES being worst affected. Children below the ages of 18 years, females, urban residents and those with higher education and SES were significantly more likely to be enrolled with the scheme. Conclusions Despite the introduction of policy exemptions as an equity measure, the poorest of the poor were rarely identified for exemption. The government must urgently resource the Department of Social Welfare to identify the poor for NHIS enrollment.