BackgroundSET domain bifurcated 1 (SETDB1) has been widely considered as an oncogene playing a critical role in many human cancers, including breast cancer. Nevertheless, the molecular mechanism by which SETDB1 regulates breast cancer tumorigenesis is still unknown.MethodsqRT-PCR assay or western blot analysis was performed to assess the expression level of SETDB1 mRNA or protein, respectively. siSETDB1, pCMV6-XL5-SETDB1, miR-381-3p mimic, or miR-381-3p inhibitor was transfected into cells to regulate the expression of SETDB1 or miR-381-3p. MiRNA directly interacted with SETDB1 was verified by luciferase reporter assay and RNA immunoprecipitation. CCK-8 assay, colony formation assay, flow cytometric analysis, and transwell assay were used to detect the abilities of cell proliferation, cell cycle progression and migration, respectively. Animal model of xenograft tumor was used to observe the regulatory effect of SETDB1 on tumor growth in vivo.ResultsWe verified that SETDB1 mRNA level was upregulated in breast cancer tissues and cell lines, and SETDB1 depletion led to a suppression of cell proliferation, cell cycle progression and migration in vitro, as well as tumor growth in vivo. SETDB1 was verified to be a target of miR-381-3p. Moreover, miR-381-3p overexpression suppressed cell proliferation, cell cycle progression and migration, whereas SETDB1 abated miR-381-3p-mediated regulatory function on breast cancer cells.ConclusionsThis study revealed that SETDB1 knockdown might suppress breast cancer progression at least partly by miR-381-3p-related regulation, providing a novel prospect in breast cancer therapy.

This study aimed to determine the role of plasma miR-17-92 cluster level in predicting chemoresistance in patients with gastric cancer (GC) undergoing oxaliplatin/capecitabine (XELOX) chemotherapy.Patients recently diagnosed with advanced GC were chosen as participants based on the inclusion criteria. The plasma levels of miR-17-5p, miR-18a, miR-19a/b, miR-20a, and miR-92-1 (miR-17-92 cluster) were determined through quantitative RT-PCR of blood samples from GC patients and healthy volunteers. All the patients received XELOX chemotherapy, and the effectiveness of the chemotherapy was evaluated.The miR-17-92 plasma level was increased in advanced GC patients and decreased after XELOX chemotherapy. Moreover, the miR-17-92 cluster level was associated with chemotherapy response but not with chemotherapy-related toxicity. The miR-17-92 cluster plasma level was decreased in chemosensitive patients, but not in chemoresistant patients, after chemotherapy. The sensitivity and specificity of the combined detection of the miR-17-92 cluster in patients with advanced GC were 100% each.The results suggest that the miR-17-92 plasma level is associated with the progression of advanced GC and effectiveness of XELOX chemotherapy.

Background: Gastric cancer (GC) is one of the most common malignant tumors and the second most frequent cause of cancer death worldwide. Crocin is a kind of bioactive constituent found in the stigmas of saffron, which has shown various pharmacological activities. Methods: In this study, we investigated the inhibitory effect of crocin on gastric cancer AGS cells proliferation and explored the underlying mechanism. A series of methods were used including cell counting kit assay, gene microarray analysis, qRT-PCR, Celigo image cytometry, cell clone formation assay, Western blot, and cell xenograft growth in vivo. Results: The results indicated that crocin inhibited AGS cells proliferation and promoted cell apoptosis. Further studies suggested that crocin decreased a series of genes expression, among which TPM4 gene downregulation inhibited the tumor cells proliferation and tumor growth in mice, and overexpression of TPM4 gene abolishes the inhibitory effect of crocin. Further study using microarray analysis suggested that knocking down of TPM4 altered genes related to the proliferation and apoptosis of cells. Discussion: Crocin could inhibit the gastric cancer cells AGS cells proliferation by regulating TPM4 gene expression, and TPM4 may be a promising therapeutic target for GC treatment.