ABSTRACT
Most primary breast cancers express estrogen receptor α and can be treated via endocrine therapy using anti-estrogens such as tamoxifen; however, acquired endocrine resistance is a critical issue. To identify tamoxifen response-related microRNAs (miRNAs) in breast cancer, MCF-7 cells infected with a lentiviral miRNA library were treated with 4-hydroxytamoxifen (OHT) or vehicle for 4 weeks, and the amounts of individual miRNA precursors that had integrated into the genome were evaluated by microarray. Compared to the vehicle-treated cells, 5 'dropout' miRNAs, which were downregulated in OHT-treated cells, and 6 'retained' miRNAs, which were upregulated in OHT-treated cells, were identified. Of the dropout miRNAs, we found that miR-574-3p expression was downregulated in clinical breast cancer tissues as compared with their paired adjacent tissues. In addition, anti-miR-574-3p reversed tamoxifen-mediated suppression of MCF-7 cell growth. Clathrin heavy chain (CLTC) was identified as a miR-574-3p target gene by in silico algorithms and luciferase reporter assay using the 3' untranslated region of CLTC mRNA. Interestingly, loss and gain of miR-574-3p function in MCF-7 cells causes CLTC to be upregulated and downregulated, respectively. These results suggest that functional screening mediated by miRNA libraries can provide new insights into the genes essential for tamoxifen response in breast cancer.
Subject(s)
Antineoplastic Agents, Hormonal/toxicity , Down-Regulation/drug effects , MicroRNAs/metabolism , Tamoxifen/analogs & derivatives , Up-Regulation/drug effects , 3' Untranslated Regions , Algorithms , Base Sequence , Binding Sites , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Clathrin/antagonists & inhibitors , Clathrin/genetics , Clathrin/metabolism , Female , Gene Library , Humans , MCF-7 Cells , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Oligonucleotides, Antisense/metabolism , RNA Interference , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Sequence Alignment , Tamoxifen/toxicityABSTRACT
It is known that the rate of low birth weight in African developing countries is very high. A birth weight analysis based on their delivery charts is made in this paper for the babies born from 1988 to 1990 at two maternity hospitals, Castor and Boy-Rabe, in Bangui, the capital of the Republic of Central Africa. The total number of births amounted to 27,188 for Castor and 7,667 for Boy-Rabe, excluding multiple births. As a result, it was found that the youngest mother's age was twelve and the oldest fifty three, with the average age at the first delivery seventeen, followed by the another delivery every two years. Mean birth weight (MBW) values were significantly higher in Castor (males 3,134 +/- 527.5, females 3,018 +/- 511.6 grams) than in Boy-Rabe (males 3,017 +/- 542.6, females 2,909 +/- 507.1 grams). The total rate of low birth weight (LBW) under 2,500 grams was 10.9 percent. That of Castor maternity was 9.8 percent, while it was 14.7 percent for Boy-Rabe, which is significantly higher than the former. In addition, the rate of LBW is the highest in the first delivery for mothers younger than 16, while it is the lowest in the sixth delivery of the group of mothers group aged 25-29. Looking at the seasonal variation of LBW, we noticed that it became higher in July and August every year, the busiest period for farming, with harvesting followed by planting. These findings suggest that low birth weight infants are due to the age of delivery being younger than sixteen and also to the mother's heavy labor.