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[Display omitted] • Fifteen new hecogenin–triphenylphosphonium conjugates were designed and synthesized. • The conjugates were screened for their antiproliferative activities. • Compound 3c exhibited the best inhibitory activity against human gastric cancer MKN45 cells. • Compound 3c induced MKN45 cells apoptosis through mitochondrial pathway. • Compound 3c inhibited MKN45 cells proliferation in an in vivo zebrafish xenograft model. Hecogenin (HCG), a steroidal sapogenin, possesses good antitumor properties. However, the application of HCG for cancer treatment has been hindered primarily by its moderate potency. In this study, we incorporated triphenylphosphonium cation (TPP+) at the C-3 and C-12 positions through different lengths of alkyl chains to target mitochondria and enhance the efficacy and selectivity of the parent compound. Cytotoxicity screening revealed that most of the target compounds exhibited potent antiproliferative activity against five human cancer cell lines (MKN45, A549, HCT-116, MCF-7, and HepG2). Structure-activity relationship studies indicated that the TPP+ group significantly enhanced the antiproliferative potency of HCG. Among these compounds, 3c demonstrated remarkable potency against MKN45 cells with an IC 50 value of 0.48 μM, significantly more effective than its parent compound HCG (IC 50 > 100 μM). Further investigations into the mechanism of action revealed that 3c induced apoptosis of MKN45 cells through the mitochondrial pathway. In a zebrafish xenograft model, 3c inhibited the proliferation of MKN45 cells. Overall, these results suggest that 3c , with potent antiproliferative activity, may serve as a valuable scaffold for developing new antitumor agents. [ABSTRACT FROM AUTHOR]

The implication of circular RNAs (circRNAs) in the pathogenesis of human cervical cancer (CC) has been demonstrated by numerous of researches, nevertheless, the whole regulatory network of circRNAs in CC remains unclear. In the present study, two GSE data sets (GSE113696 and GSE102686) were enrolled to analysed different expressed circRNA. We found that hsa_circ_0000520(circ_0000520) was decreased in CC tissues and cell lines. Functional studies indicated circ_0000520 overexpression in vitro repressed CC cell proliferation, invasion and migration, while promoted CC cell apoptosis. Moreover, circ_0000520 overexpression in vivo repressed CC tumour growth. Mechanismly, circ_0000520 and PAX5 were revealed to directly bind to miR‐146b‐3p, and circ_0000520 could indirectly regulate PAX5 by sponging miR‐146b‐3p. In conclusion, circ_0000520 repressed CC progression in vitro and in vivo by sponging miR‐146b‐3p to release PAX5. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) are an important biomarker for cancer prognosis and treatment monitoring. However, the heterogeneity of the physical and biological properties of CTCs limits the efficiency of various approaches used to isolate small numbers of CTCs from billions of normal blood cells. To address this challenge, we developed a lateral filter array microfluidic (LFAM) device to integrate size‐based separation with immunoaffinity‐based CTC isolation. The LFAM device consists of a serpentine main channel, through which most of a sample passes, and an array of lateral filters for CTC isolation. The unique device design produces a two‐dimensional flow, which reduces nonspecific, geometric capture of normal cells as typically observed in vertical filters. The LFAM device was further functionalized by immobilizing antibodies that are specific to the target cells. The resulting devices captured pancreatic cancer cells spiked in blood samples with (98.7±1.2) % efficiency and were used to isolate CTCs from patients with metastatic colorectal cancer. [ABSTRACT FROM AUTHOR]

We report a simple but effective strategy to capture tumor cells using fibrin-immobilized microchannels. It is a universal method since it shows an ability to capture both epithelial and mesenchymal tumor cells. The cell capture efficiency is up to 90%. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the common malignancies in women, which is characterized with high invasion and metastatic tendency in its advanced stage. Increasing evidence indicates that methyltransferase-like (METTL) gene family is involved in the progression of various cancers. However, the functional role of methyltransferase-like gene family in cervical cancer remains unclear. In the present study, we found that METTL11A, a member of the methyltransferase-like gene family, was significantly over-expressed in cervical carcinoma by analyzing TCGA database. This finding was further validated in clinical tissue samples. Moreover, ectopic expression of METTL11A in cervical cancer cell lines promoted cell proliferation and migration both in vitro and in vivo. Differential gene expression analysis in the transcriptomic sequencing data indicated that ELK3 was down-regulated in METTL11A-silenced cervical cancer cells, which was further verified at both protein and mRNA levels. Functional experiments identified that METTL11A promoted migration of cervical cancer cells in an ELK3-dependent manner. This study will promote understanding the mechanism of cervical cancer progression and the functional role of methyltransferase-like gene families in cancers. [Display omitted] • METTL11A is positively correlated with progression of cervical cancer. • METTL11A serves as a potential target for the diagnosis and prognosis of cervical cancer. • METTL11A significantly promotes cell proliferation and cell migration both in vivo and in vitro. • METTL11A promotes the migration of cervical cancer cells by up-regulating ELK3. [ABSTRACT FROM AUTHOR]

The methods for isolating rare cells such as circulating tumor cells (CTCs) can be generally classified into two categories: those based on physical properties (e.g., size) and methods based on biological properties (e.g., immunoaffinity). CellSearch, the only FDA-approved method for the CTC-based cancer prognosis, relies on immunoaffinity interactions between CTCs and antibodies immobilized on magnetic particles. Immunoaffinity-based CTC isolation has also been employed in microfluidic devices, which show higher capture efficiency than CellSearch. We report here our investigation of combining size-based microfiltration into a microfluidic device with immunoaffinity for enhanced capture efficiency of CTCs. The device consists of four serpentine main channels, and each channel contains an array of lateral filters that create a two-dimensional flow. The main flow is through the serpentine channel, allowing the majority of the sample to pass by while the secondary flow goes through the lateral filters. The device design is optimized to make all fluid particles interact with filters. The filter sizes range from 24 to 12 µm, being slightly larger than or having similar dimension of CTCs. These filters are immobilized with antibodies specific to CTCs and thus they function as gates, allowing normal blood cells to pass by while forcing the interactions between CTCs and antibodies on the filter surfaces. The hydrodynamic force experienced by a CTC was also studied for optimal experimental conditions to ensure immunoaffinity-enabled cell capture. The device was evaluated by capturing two types of tumor cells spiked in healthy blood or a buffer, and we found that their capture efficiency was between 87.2 and 93.5%. The platform was further validated by isolating CTCs from blood samples of patients with metastatic pancreatic cancer. [ABSTRACT FROM AUTHOR]