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This network meta-analysis compared the short-term and long-term efficacies of first-line chemotherapy regimens in patients with advanced colorectal cancer (CRC). The 10 regimens included folinic acid + 5-fluorouracil + oxaliplatin (FOLFOX), folinic acid + 5-fluorouracil + irinotecan (FOLFIRI), folinic acid + 5-fluorouracil + gemcitabine (FFG), folinic acid + 5-fluorouracil + trimetrexate (FFT), folinic acid + 5-fluorouracil (FF), irinotecan + oxaliplatin (IROX), raltitrexed + oxaliplatin (TOMOX), folinic acid + tegafur-uracil (FTU), raltitrexed, and capecitabine. Electronic searches were performed in the Cochrane Library, PubMed and Embase databases from inception to June 2017. Network meta-analysis combined direct and indirect evidence to obtain odds ratios (ORs) and surface under the cumulative ranking curves (SUCRA) of different chemotherapy regimens for advanced CRC. Fourteen randomized controlled trails (RCTs) covering 4,383 patients with advanced CRC were included. The results revealed that FOLFOX, FOLFIRI, IROX, and TOMOX all showed higher overall response rates (ORRs) than FF or raltitrexed. Compared with raltitrexed, the aforementioned four regimens also had higher 1-year progression-free survival (PFS) rates. In addition, FOLFOX and FOLFIRI exhibited higher disease control rates (DCRs) and 1-year PFS rates than FF or raltitrexed. Cluster analysis revealed that FOLFOX, FOLFIRI, and TOMOX had better short-term and long-term efficacies. These findings suggest FOLFOX, FOLFIRI, and TOMOX are superior to other regimens for advanced CRC. These three regimens are therefore recommended for clinical treatment of advanced CRC., Competing Interests: CONFLICTS OF INTEREST There was no conflicts of interest existing in this paper.

We investigated the involvement of microRNA-433 (miR-433) in the proliferation, migration, and invasiveness of oral squamous cell carcinoma (OSCC). Totally 108 OSCC tissues and adjacent normal tissues from patients with OSCC were collected. Also, transplanted tumor formation experiment in nude mice was conducted to verify the effect of miR-433 and FAK on subcutaneous transplanted tumor. The CD44 + stem cell from SCC-9 were collected and assigned into the blank, miR-433 mimics, mimics control, miR-433 inhibitors, inhibitors control, siFAK and miR-433 inhibitors + siFAK groups. The qRT-PCR and western blotting were used to detect miR-433, FAK, ERK, MEK, pERK and pMEK after transfection. Flow cytometry, MTT assay, scratch test and Transwell assay were performed to determine the cell proportion, growth, migration and invasion of SCC-9 cells. In cell line SCC-9, expression of CD133, Oct-4, and BIM-1 was greater in CD44 + cells than CD44 - cells, indicating that CD44 + cells had characteristics of tumor stem cells. Expression of FAK, ERK, MEK, p-ERK and p-MEK was decreased in tumor tissues from the CD44 - , miR-433, and siFAK groups. Expression of MiR-433 mRNA was elevated, while levels of FAK, ERK, MEK, p-ERK, and p-MEK mRNA were all decreased in the miR-433 mimics group. In the miR-433 mimics and siFAK groups, cell proliferation, migration, and invasion were all decreased, while the opposite trends were seen in the miR-433 inhibitor group. These results indicate that miR-433 downregulates FAK through the ERK/MAPK signaling pathway to inhibit the proliferation, migration, and invasiveness of SCC-9 OSCC cells., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Intrauterine growth retardation (IUGR) is a common obstetric complication lacking an optimal method for prenatal screening. DNA methylation profile in maternal blood holds significant promise for prenatal screening. Here, we aimed to screen out potential IUGR biomarkers in maternal blood from the perspective of DNA methylation. The IUGR rat model was established by prenatal maternal undernutrition. High-throughput bisulfite sequencing of genomic DNA methylation followed by functional clustering analysis for differentially methylated region (DMR)-associated genes demonstrated that genes regulating transcription had the most significantly changed DNA methylation status in maternal blood with IUGR. Genes about apoptosis and placental development were also changed. Besides increased placental apoptosis, IUGR rats demonstrated the same hypermethylated CpG sites of steroidogenic factor-1 (SF-1, a DMR-associated transcription factor about placenta) promoter in maternal blood and placentae. Further, ff1b, the SF-1 ortholog, was knocked out in zebrafish by CRISPR/Cas9 technology. The knock-out zebrafish demonstrated developmental inhibition and increased IUGR rates, which confirmed the role of SF-1 in IUGR development. Finally, hypermethylated SF-1 was observed in human maternal blood of IUGR. This study firstly presented distinct DNA methylation profile in maternal blood of IUGR and showed hypermethylated SF-1 could be a potential IUGR biomarker in maternal rat blood., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest were disclosed.

We investigated the mechanisms by which microRNA (miR)-182 promotes apoptosis and inhibits proliferation in human osteosarcoma (OS) cells. Levels of miR-182 and Homeobox A9 (HOXA9) expression were compared between human OS and normal cells. Subjects were divided into OS and normal groups. We analyzed the target relationship of miR-182 and Homeobox A9 (HOXA9). Cells were then assigned into blank, negative control, miR-182 mimics, miR-182 inhibitors, siRNA-HOXA9, or and miR-182 inhibitors + siRNA-HOXA9 groups. Cell function was assayed by CCK-8, flow cytometry and wound healing assay. Additionally, we analyzed OS tumor growth in a xenograft mouse model. Dual-luciferase reporter assays indicated miR-182 directly targets HOXA9. Reverse transcription quantitative PCR and western blotting revealed elevated expression of miR-182, WIF-1, BIM, and Bax, and reduced expression of HOXA9, Wnt, β-catenin, Survivin, Cyclin D1, c-Myc, Mcl-1, Bcl-xL, and Snail in osteosarcoma cells treated with miR-182 mimic or siRNA-HOXA9 as compared to controls. Osteosarcoma cells also exhibited decreased cell proliferation, migration, and tumor growth, and increased apoptosis when treated with miR-182 mimic or siRNA-HOXA9. Correspondingly, in a xenograft mouse model, osteosarcoma tumor volume and growth were increased when cells were treated with miR-182 inhibitor and decreased by miR-182 mimic or siRNA-HOXA9. These results indicate that miR-182 downregulates Wnt/β-catenin signaling, inhibits cell proliferation, and promotes apoptosis in osteosarcoma cells by suppressing HOXA9 expression., Competing Interests: CONFLICTS OF INTEREST The authors declare that there are no conflicts of interest.

Human 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) is the gene identified from adipose tissue in 2007. We found AGPAT9 expression was significantly higher in poorly invasive MCF7 human breast cancer cells than the highly invasive MDA-MB-231 cells. AGPAT9 significantly inhibited the proliferation of breast cancer cells in vitro and in vivo. Live-cell imaging and transwell assays showed that AGPAT9 could significantly inhibit the migration and invasive capacities of breast cancer cells. The inhibitory effect of AGPAT9 on metastasis was also observed in vivo in lung metastasis model. AGPAT9 inhibited breast cancer cell proliferation, migration and invasion through, at least in part, suppressing the V-ATPase activity. In addition, increased AGPAT9 expression in MCF-7/ADR cells could increase the chemosensitivity to doxorubicin (Dox). Our findings suggest that increasing AGPAT9 expression may be a new approach that can be used for breast cancer treatment.