The emerging roles and therapeutic potential of cyclin-dependent kinase 11 (CDK11) in human cancer.

Overexpression and/or hyperactivation of cyclin-dependent kinases (CDKs) are common features of most cancer types. CDKs have been shown to play important roles in tumor cell proliferation and growth by controlling cell cycle, transcription, and RNA splicing. CDK4/6 inhibitor palbociclib has been recently approved by the FDA for the treatment of breast cancer. CDK11 is a serine/threonine protein kinase in the CDK family and recent studies have shown that CDK11 also plays critical roles in cancer cell growth and proliferation. A variety of genetic and epigenetic events may cause universal overexpression of CDK11 in human cancers. Inhibition of CDK11 has been shown to lead to cancer cell death and apoptosis. Significant evidence has suggested that CDK11 may be a novel and promising therapeutic target for the treatment of cancers. This review will focus on the emerging roles of CDK11 in human cancers, and provide a proof-of-principle for continued efforts toward targeting CDK11 for effective cancer treatment

Radial free forearm flap versus pectoralis major pedicled flap for reconstruction in patients with tongue cancer : assessment of quality of life

This study investigated the quality of life of Chinese patients with tongue cancer who had undergone immediate flap reconstruction surgery. In addition, we compared 2 groups of patients: those who had received radial forearm free flap (RFFF) surgery and others who had received pectoralis major myocutaneous flap (PMMF) surgery. Patients who received RFFF or PMMF reconstruction after primary tongue cancer treated with total and subtotal tongue resection were eligible for the current study. The patients? demographic data, medical history, and quality of life scores (14-item Oral Health Impact Profile (OHIP-14) and the University of Washington Quality of Life (UW-QOL) questionnaires) were collected. A total of 41 of 63 questionnaires were returned (65.08%). There were significant differences between the 2 groups in the gender (p< .05). Patients reconstructed with RFFF performed better in the shoulder domains, in addition to worse appearance domains. Using either RFFF or PMMF for reconstruction of defects after tongue cancer resection significantly influences a patient?s quality of life. Data from this study provide useful information for physicians and patients during their discussion of reconstruction modalities for tongue cancers

Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome

Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell–cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as ‘synthetic stem cells’ which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration

Novel strategies to prevent the development of multidrug resistance (MDR) in cancer

The development of multidrug resistance (MDR) is one of the major challenges to the success of traditional chemotherapy treatment in cancer patients. Most studies to date have focused on strategies to reverse MDR following its development. However, agents utilizing this approach have proven to be of limited clinical use, failing to demonstrate an improvement in therapeutic efficacy with almost no significant survival benefits observed in cancer clinical trials. An alternative approach that has been applied is to prevent or delay MDR prior or early in its development. Recent investigations have shown that preventing the emergence of MDR at the onset of chemotherapy treatment, rather than reversing MDR once it has developed, may assist in overcoming drug resistance. In this review, we focus on a number of novel strategies used by small-molecule inhibitors to prevent the development of MDR. These agents hold great promise for prolonging the efficacy of chemotherapy treatment and improving the clinical outcomes of patients with cancers that are susceptible to MDR development

High miR-3609 expression is associated with better prognosis in TNBC based on mining using systematic integrated public sequencing data

MicroRNAs (miRNAs/miRs) are small endogenous RNAs that regulate gene expression post-transcriptionally. Abnormal miR-3609 expression is associated with the occurrence of pancreatic cancer, glioma and other diseases, such as polycystic ovary syndrome. However, the prognostic potential of miR-3609 has been reported in breast cancer. Thus, the present study aimed to investigate the differential expression and prognostic value of miR-3609 in patients with breast cancer from the UALCAN, cBioportal and Kaplan-Meier Plotter databases, respectively. Furthermore, the co-expression genes of miR-3609 in breast cancer were investigated using data from the LinkedOmics database, and functional enrichment analysis was performed using the LinkInterpreter module in LinkedOmics. The co-expression gene network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database, and the cytoHubba plug-in was used to identify the hub genes, which were visualized using Cytoscape software. The prognoses of the hub genes were performed using the Kaplan-Meier Plotter database. The Cell Counting Kit-8 and cell cycle assays were performed to confirm the functions of miR-3609 mimics transfection in MDA-MB-231 cells. Survival analysis using the Kaplan-Meier Plotter database demonstrated that high miR-3609 expression in triple-negative breast cancer (TNBC) was associated with a better prognosis. Furthermore, the experimental results indicated that high miR-3609 expression inhibited the proliferation of TNBC cells and induced cell cycle arrest of TNBC cells in the G 0 /G 1 phase. Taken together, the results of the present study suggest that miR-3609 plays a vital role in mediating cell cycle arrest and inhibiting the proliferation of TNBC cells

The emerging roles and therapeutic potential of cyclin-dependent kinase 11 (CDK11) in human cancer.

Overexpression and/or hyperactivation of cyclin-dependent kinases (CDKs) are common features of most cancer types. CDKs have been shown to play important roles in tumor cell proliferation and growth by controlling cell cycle, transcription, and RNA splicing. CDK4/6 inhibitor palbociclib has been recently approved by the FDA for the treatment of breast cancer. CDK11 is a serine/threonine protein kinase in the CDK family and recent studies have shown that CDK11 also plays critical roles in cancer cell growth and proliferation. A variety of genetic and epigenetic events may cause universal overexpression of CDK11 in human cancers. Inhibition of CDK11 has been shown to lead to cancer cell death and apoptosis. Significant evidence has suggested that CDK11 may be a novel and promising therapeutic target for the treatment of cancers. This review will focus on the emerging roles of CDK11 in human cancers, and provide a proof-of-principle for continued efforts toward targeting CDK11 for effective cancer treatment

Regulation of microRNA-1 (miR-1) expression in human cancer

MicroRNAs (miRs) have been found to play important roles in tumorigenesis, apoptosis, metastasis, and drug resistance in cancer. Among a number of miRs, miR-1 was shown to be predominantly downregulated in almost all examined human cancers. As a tumor suppressor miR involved in post-transcriptional regulation of crucial tumor associated gene expression, miR-1 represents a promising target for anticancer therapy. Re-expression of miR-1 can suppress cancer cell proliferation, promote apoptosis, and reverse drug resistance in cancers both in vitro and in vivo. Recently, the regulatory mechanisms of miR-1 expression have been studied in various cancers in different model systems. In this review, we summarize the mechanisms of miR-1 expression through epigenetic, transcriptional, and post-transcriptional regulation. These regulatory mechanisms of miR-1 expression could help us to understand the functions of altered miR-1 expression and provide valuable insights for further investigations into miR-1 based cancer therapy. •Expression of mircoRNA-1 (miR-1) is decreased in the majority of human cancers.•Epigenetic changes including DNA methylation may play a role in miR-1 expression.•Transcriptional and post-transcriptional changes may also regulate miR-1 expression

Regulation of microRNAs function by circular RNAs in human cancer

Circular RNAs (circRNAs) are a newly validated class of endogenous non-coding RNA, generated from the ligation of exons, introns, or both, which arise via a diverse number of cellular mechanisms. Due to rapid advances in the development of combined high-throughput sequencing and bioinformatics analyzing tools, many circRNAs have recently been discovered, revealing an expansive number of ubiquitously expressed mammalian circRNAs. Interestingly, it has recently been confirmed that circRNAs bind to microRNAs (miRs), as miR “sponges”, acting to suppress miR function. As miRs are known to alter the development and progression of cancer, circRNAs may offer a novel diagnostic and prognostic biomarker for cancer. Indeed, recent evidence has shown that circRNAs are associated with many human cancers. Herein, we review the molecular characteristics and biogenesis of circRNAs, with a focus on newly identified circRNAs that may play an important role in human cancer, through their regulation of miR expression