Cervical cancer is one of the most common gynecological malignant tumors worldwide, for which chemotherapeutic strategies are limited due to their non-specific cytotoxicity and drug resistance. The natural product thymoquinone (TQ) has been reported to target a vast number of signaling pathways in carcinogenesis in different cancers, and hence is regarded as a promising anticancer molecule. Inhibition of epithelial to mesenchymal transition (EMT) regulators is an important approach in anticancer research. In this study, TQ was used to treat the cervical cancer cell lines SiHa and CaSki to investigate its effects on EMT-regulatory proteins and cancer metastasis. Our results showed that TQ has time-dependent and dose-dependent cytotoxic effects, and it also inhibits the migration and invasion processes in different cervical cancer cells. At the molecular level, TQ treatment inhibited the expression of Twist1, Zeb1 expression, and increased E-Cadherin expression. Luciferase reporter assay showed that TQ decreases the Twist1 and Zeb1 promoter activities respectively, indicating that Twist1 and Zeb1 might be the direct target of TQ. TQ also increased cellular apoptosis in some extent, but apoptotic genes/proteins we tested were not significant affected. We conclude that TQ inhibits the migration and invasion of cervical cancer cells, probably via Twist1/E-Cadherin/EMT or/and Zeb1/E-Cadherin/EMT, among other signaling pathways.
To develop an effective strategy to isolate and use cell-free fetal DNA (cffDNA) for the combined use of next-generation sequencing (NGS) for diagnosing choroideremia and non-invasive prenatal testing (NIPT) for Y chromosome determination, a large Chinese family with an X-linked recessive disease, choroideremia, was recruited. Cell-free DNA was extracted from maternal plasma, and SRY polymerase chain reaction amplification was performed using NIPT. Sanger sequencing was subsequently used for fetal amniotic fluid DNA verification. A nonsense mutation (c.C799T:p.R267X) of the CHM gene on the X chromosome of the proband (IV:7) and another 5 males with choroideremia were detected, while 3 female carriers with no symptoms were also identified. The fetus (VI:7) was identified as female from the cffDNA, and the same heterozygous nonsense mutation present in her mother was also confirmed. At one and a half years of age, the female baby did not present with any associated symptoms of choroideremia. Therefore, cffDNA was successfully used for the combined use of NGS for diagnosing choroideremia in a large Chinese pedigree, and NIPT for Y chromosome determination. This approach should result in a markedly increased use of prenatal diagnosis and improvement, and more sophisticated clinical management of diseases in China and other developing countries. The establishment of a highly accurate method for prenatal gene diagnosis will allow for more reliable gene diagnosis, improved genetic counseling, and personalized clinical management of our patients.
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