UHRF1 predicts poor prognosis by triggering cell cycle in lung adenocarcinoma

Accumulating evidence suggests that ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) is overexpressed in non-small cell lung cancer (NSCLC); however, the expression and function of UHRF1 in the subtype of NSCLC are still unclear. Here, we investigate the expression and prognosis traits of UHRF1 in large NSCLC cohorts and explore the molecular characters during UHRF1 up-regulation. We find that UHRF1 is predominantly overexpressed in lung squamous cell carcinoma (SCC). Surprisingly, the up-regulated UHRF1 is only associated with the overall survival of lung adenocarcinoma (ADC) and knockdown of UHRF1 dramatically attenuates ADC tumorigenesis. Mechanically, we identify a hub gene that includes a total of 55 UHRF1-related genes, which are tightly associated with cell cycle pathway and yield to the poor clinical outcome in ADC patients. What's more, we observe knockdown of UHRF1 only affects ADC cells cycle and induces cell apoptosis. These results suggest that up-regulated UHRF1 only contributes to lung ADC survival by triggering cell cycle pathway, and it may be a prognostic biomarker for lung ADC patients.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

CC Chemokine Ligand-2: A Promising Target for Overcoming Anticancer Drug Resistance

CC chemokine ligand-2 (CCL2), a proinflammatory chemokine that mediates chemotaxis of multiple immune cells, plays a crucial role in the tumor microenvironment (TME) and promotes tumorigenesis and development. Recently, accumulating evidence has indicated that CCL2 contributes to the development of drug resistance to a broad spectrum of anticancer agents, including chemotherapy, hormone therapy, targeted therapy, and immunotherapy. It has been reported that CCL2 can reduce tumor sensitivity to drugs by inhibiting drug-induced apoptosis, antiangiogenesis, and antitumor immunity. In this review, we mainly focus on elucidating the relationship between CCL2 and resistance as well as the underlying mechanisms. A comprehensive understanding of the role and mechanism of CCL2 in anticancer drug resistance may provide new therapeutic targets for reversing cancer resistance

The Role of H2-Calponin Antigen in Cancer Metastasis: Presence of Autoantibodies in Liver Cancer Patients

To investigate the potential of H2-calponin (CNN2) as a serum biomarker for hepatocellular carcinoma (HCC), this study employed the serological analysis of recombinantly expressed cDNA clone (SEREX) technique to identify the presence of CNN2 antibody in the serum of patients with HCC and other tumors. The CNN2 protein was produced through genetic engineering and used as an antigen to determine the positive rate of serum CNN2 autoantibodies via indirect enzyme-linked immunosorbent assay (ELISA). In addition, the mRNA and protein expressions of CNN2 in cells and tissues were evaluated using RT-PCR, in situ RT-PCR, and immunohistochemistry methods. The HCC group exhibited a significantly higher positive rate of anti-CNN2 antibody (54.8%) compared to gastric cancer (6.5%), lung cancer (3.2%), rectal cancer (9.7%), hepatitis (3.2%), liver cirrhosis (3.2%), and normal tissues (3.1%). The positive rates of CNN2 mRNA in HCC with metastasis, non-metastatic HCC, lung cancer, gastric cancer, nasopharyngeal cancer, liver cirrhosis, and hepatitis were 56.67%, 41.67%, 17.5%, 10.0%, 20.0%, 53.13%, and 41.67%, respectively. Meanwhile, the positive rates of CNN2 protein were 63.33%, 37.5%, 17.5%, 27.5%, 45%, 31.25%, and 20.83%, respectively. The down-regulation of CNN2 could inhibit the migration and invasion of liver cancer cells. CNN2 is a newly identified HCC-associated antigen that is implicated in the migration and invasion of liver cancer cells, making it a promising target for liver cancer therapy

CCR9 in cancer: oncogenic role and therapeutic targeting

Abstract Cancer is currently one of the leading causes of death worldwide and is one of the most challenging major public health problems. The main challenges faced by clinicians in the management and treatment of cancer mainly arise from difficulties in early diagnosis and the emergence of tumor chemoresistance and metastasis. The structures of chemokine receptor 9 (CCR9) and its specific ligand chemokine ligand 25 (CCL25) have been elucidated, and, interestingly, a number of studies have demonstrated that CCR9 is a potential tumor biomarker in diagnosis and therapy, as it has been found to be highly expressed in a wide range of cancers. This expression pattern suggests that CCR9 may participate in many important biological activities involved in cancer progression. Researchers have shown that CCR9 that has been activated by its specific ligand CCL25 can interact with many signaling pathways, especially those involved in tumor chemoresistance and metastasis. This review, therefore, focuses on CCR9 induction activity and summarizes what is currently known regarding its role in cancers and its potential application in tumor-targeted therapy

Uncovering the roles of long non-coding RNAs in cancer stem cells

Abstract Cancer has been a major public health problem that has threatened human life worldwide throughout history. The main causes that contribute to the poor prognosis of cancer are metastasis and recurrence. Cancer stem cells are a group of tumor cells that possess self-renewal and differentiation ability, which is a vital cause of cancer metastasis and recurrence. Long non-coding RNAs refer to a class of RNAs that are longer than 200 nt and have no potential to code proteins, some of which can be specifically expressed in different tissues and different tumors. Long non-coding RNAs have great biological significance in the occurrence and progression of cancers. However, how long non-coding RNAs interact with cancer stem cells and then affect cancer metastasis and recurrence is not yet clear. Therefore, this review aims to summarize recent studies that focus on how long non-coding RNAs impact tumor occurrence and progression by affecting cancer stem cell self-renewal and differentiation in liver cancer, prostate cancer, breast cancer, and glioma

Sandwich-Structured MXene/Carbon Hybrid Support Decorated with Pt Nanoparticles for Oxygen Reduction Reaction

Carbon supports for cathodic catalysts in proton-exchange membrane fuel cells suffer from rapid corrosion and instability; therefore, alternative supports with a stable structure and a high electric conductivity are highly required. In this paper, a three-dimensional support hybridized by MXene and Ketjen Black is developed, in which Ketjen Black is sandwiched between MXene nanosheets (MCM). After decorating with Pt nanoparticles by a facile wet-chemical approach, a three-dimensional (3D) Pt/MCM catalyst is obtained. The intercalated Ketjen Black prevents the stacking of MXene nanosheets, thus increasing the specific surface area of the catalyst and exposing the active sites. The strong interaction between functionalized MXene nanosheets and Pt nanoparticles further enhances its intrinsic electrocatalytic activity. Pt/MCM demonstrated encouraging ORR activity with the half-wave potential and specific activity of 0.892 V and 0.377 mA·cm–2, respectively, surpassing the state-of-the-art Pt/C catalysts. Especially, Pt/MCM achieves ultrahigh durability with a 1 mV decrease in half-wave potential and a 1.73% decrease in mass activity after an accelerated durability test. Given the performance and structure–activity relationships of Pt/MCM, it holds great potential for various energy and catalysis-related applications

FANCD2 and REV1 cooperate in the protection of nascent DNA strands in response to replication stress

REV1 is a eukaryotic member of the Y-family of DNA polymerases involved in translesion DNA synthesis and genome mutagenesis. Recently, REV1 is also found to function in homologous recombination. However, it remains unclear how REV1 is recruited to the sites where homologous recombination is processed. Here, we report that loss of mammalian REV1 results in a specific defect in replication-associated gene conversion. We found that REV1 is targeted to laser-induced DNA damage stripes in a manner dependent on its ubiquitin-binding motifs, on RAD18, and on monoubiquitinated FANCD2 (FANCD2-mUb) that associates with REV1. Expression of a FANCD2-Ub chimeric protein in RAD18-depleted cells enhances REV1 assembly at laser-damaged sites, suggesting that FANCD2-mUb functions downstream of RAD18 to recruit REV1 to DNA breaks. Consistent with this suggestion we found that REV1 and FANCD2 are epistatic with respect to sensitivity to the double-strand break-inducer camptothecin. REV1 enrichment at DNA damage stripes also partially depends on BRCA1 and BRCA2, components of the FANCD2/BRCA supercomplex. Intriguingly, analogous to FANCD2-mUb and BRCA1/BRCA2, REV1 plays an unexpected role in protecting nascent replication tracts from degradation by stabilizing RAD51 filaments. Collectively these data suggest that REV1 plays multiple roles at stalled replication forks in response to replication stress

Additional file 1: of Uncovering the roles of long non-coding RNAs in cancer stem cells

Summary of LncRNAs related pathways in Hepatocellular carcinoma, Prostate cancer, Breast cancer, and Glioma. (XLSX 9 kb