Lung cancer continues to be a prevalent cause of cancer-related deaths worldwide, with lung squamous carcinoma (LUSC) being a significant subtype characterized by comparatively low survival rates. Extensive molecular studies on LUSC have been conducted; however, the clinical importance of cell-cycle-associated genes has rarely been examined. This study aimed to investigate the relationship between these genes and LUSC.
The expression trends of genes related to the cell cycle in a group of patients with LUSC were analyzed. Clinical information and mRNA expression data were obtained from The Cancer Genome Atlas via cBioportal. Multiple analyses have been performed to investigate the association between these genes and LUSC.
Three clusters were identified based on the mRNA expression of 124 cell cycle-associated genes. Cluster 3 exhibited the worst prognosis. A comparative analysis showed that nine expressed genes differed distinctly among all the clusters. Among these nine genes, elevated expression of CDK4 was strongly associated with positive prognosis. Furthermore, the expression of ANAPC11, ANAPC5, and ORC4 correlated with the advancement of LUSC pathological stages.
Gene expression profiles associated with the cell cycle across various LUSC subtypes were identified, highlighting that specific genes are related to prognosis and disease stages. Based on these results, new prognostic strategies, patient stratification, and targeted therapy trials have been conducted for LUSC.
Conventional adeno-associated viral (AAV) vectors, while highly effective in quiescent cells such as hepatocytes in the adult liver, confer less durable transgene expression in proliferating cells owing to episome loss. Sustained therapeutic success is therefore less likely in liver disorders requiring early intervention. We have previously developed a hybrid, dual virion approach, recombinant AAV (rAAV)/piggyBac transposon system capable of achieving stable gene transfer in proliferating hepatocytes at levels many fold above conventional AAV vectors. An alternative transposon system, Sleeping Beauty, has been widely used for ex vivo gene delivery; however liver-targeted delivery using a hybrid rAAV/Sleeping Beauty approach remains relatively unexplored.
We investigated the capacity of a Sleeping Beauty (SB)-based dual rAAV virion approach to achieve stable and efficient gene transfer to the newborn murine liver using transposable therapeutic cassettes encoding coagulation factor IX or ornithine transcarbamylase (OTC).
At equivalent doses, rAAV/SB100X transduced hepatocytes with high efficiency, achieving stable expression into adulthood. Compared with conventional AAV, the proportion of hepatocytes transduced, and factor IX and OTC activity levels, were both markedly increased. The proportion of hepatocytes stably transduced increased 4- to 8-fold from <5%, and activity levels increased correspondingly, with markedly increased survival and stable urinary orotate levels in the OTC-deficient Spfash mouse following elimination of residual endogenous murine OTC.
The present study demonstrates the first in vivo utility of a hybrid rAAV/SB100X transposon system to achieve stable long-term therapeutic gene expression following delivery to the highly proliferative newborn mouse liver. These results have relevance to the treatment of genetic metabolic liver diseases with neonatal onset.
The uncontrolled growth and spread of cancerous cells beyond their usual boundaries into surrounding tissues characterizes cancer. In developed countries, cancer is the leading cause of death, while in underdeveloped nations, it ranks second. Using existing cancer diagnostic tools has increased early detection rates, which is crucial for effective cancer treatment. In recent decades, there has been significant progress in cancer-specific survival rates owing to advances in cancer detection and treatment. The ability to accurately identify precursor lesions is a crucial aspect of effective cancer screening programs, as it enables early treatment initiation, leading to lower long-term incidence of invasive cancer and improved overall prognosis. However, these diagnostic methods have limitations, such as high costs and technical challenges, which can make accurate diagnosis of certain deep-seated tumors difficult. To achieve accurate cancer diagnosis and prognosis, it is essential to continue developing cutting-edge technologies in molecular biology and cancer imaging.
Identifying biomarkers to predict immune checkpoint inhibitor (ICI) efficacy is warranted. Considering that somatic mutation-derived neoantigens induce strong immune responses, patients with a high tumor mutational burden reportedly tend to respond to ICIs. Therefore, the original function of neoantigenic mutations and their impact on the tumor microenvironment (TME) require attention. RNF43 is a type of RING E3 ubiquitin ligase, and long-term survivors in most cancers had conserved patterns of mutations of RNF43. Also, high microsatellite instability patients had a higher RNF43 mutation rate compared with microsatellite stability tumor patients, who were more sensitive to ICI treatment. Therefore, RNF43 has become a promising biomarker of immunotherapy in a wide range of cancers. This review focuses on the up-to-date knowledge of RNF43 mutation in cancer. We summarize the cancer hallmarks involving activities regulated by RNF43 and highlight its extremely sophisticated regulation of WNT signaling and tumor microenvironment. The key genes interacting with RNF43 have also been summarized and discussed. Additionally, we highlight and propose new strategies of targeting RNF43 and RNF43-based combinations with established immunotherapy and combination therapy. These efforts may provide new perspectives for RNF43-based target therapy in cancer.
Endoplasmic reticulum stress (ERS) could be a strategy for treating malignant tumors. Moreover, long noncoding RNAs (lncRNAs) can promote tumorigenesis and progression, and forecast the prognosis of cancers. Nevertheless, the prognostic value of ERS-related lncRNAs has not been reported in lung adenocarcinoma (LUAD).
The messenger RNA (mRNA), microRNA (miRNA) and lncRNA expression data related to LUAD were obtained in public databases (TCGA and GEO databases). Prognostic ERS-related differentially expressed lncRNAs (ERS-DELs) were obtained and used to build an ERS-related model by Cox regression analysis. Moreover, we further screened independent prognostic elements and built a nomogram. Furthermore, enrichment analysis of genes was conducted to investigate the functions. A lncRNA–miRNA–mRNA network was built to explore mechanism of lncRNAs. Finally, qRT-PCR was utilized to examine the expression levels of lncRNAs.
30 ERS-DELs were identified, and an ERS-related signature was built based on AF131215.2, LINC00472, LINC01352, RP1-78O14.1, RP11-253E3.3, RP11-98D18.9, and SNHG12. Gene set enrichment analysis indicated that genes in the high-risk group were chiefly focused on the regulation of mRNA binding, and genes in the low-risk group were significantly focused on protein localization to cilia. A lncRNA–miRNA–mRNA network, containing 7 signature lncRNAs, 23 miRNAs, and 128 mRNAs, was also established. Eventually, quantitative real-time polymerase chain reaction was used to confirm that seven prognostic lncRNAs had a consistent expression with the analysis.
An ERS-related signature containing seven prognostic lncRNAs was built, which offered new thinking concerning the role of ERS-related lncRNAs in LUAD.
Esophageal cancer is one of the major cancers in China. Most patients with esophageal cancer are diagnosed at an advanced stage, and the 5 year survival rate is discouraging. Combined chemotherapy is a common method for the treatment of esophageal cancer.
In this study, distearoyl phosphatidyl ethanolamine polyethylene glycol 2000 (DSPE-PEG2000) nanoliposomes (NLPs) encapsulating the anticancer drugs docetaxel (DOX) and oridonin (ORD) were prepared, and their ability to enhance the release of anticancer drugs was determined. The NLP system was characterized by transmission electron microscopy, particle size and encapsulation efficiency. In addition, the release characteristics and pharmacodynamics of these drugs were also studied in detail.
When the DOX/ORD ratio was 2:1, the higher proportion of DOX led to a stronger synergy effect. DOX/ORD NLPs were prepared by the high-pressure homogenization method and had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 246.4 and 0.163, respectively. The stability results showed that no significant change was observed in particle size, zeta potential, Encapsulation efficiency and dynamic light scattering for DOX/ORD NLPs during the observation period. The results of in vitro release illustrated that the acidic environment of tumor might be beneficial to drug release. The three-dimensional tumorsphere showed that DOX/ORD NLPs can reach the interior of tumor spheres, which destroys the structure of cells, resulting in irregular spherical tumor spheres. The in vivo study results indicated that DOX/ORD NLPs had an obvious targeting effect on subcutaneous tumors and have the potential to actively deliver drugs to tumor tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to detect apoptosis. The results showed that DOX/ORD NLP treatment could significantly induce apoptosis and inhibit tumor growth.
The DOX/ORD NLPs prepared in this study can enhance the anti-tumor activity, and are expected to be a promising co-delivery platform for the treatment of esophageal cancer.
RETRACTION: X. Zhong, X. Wen, L. Chen, N. Gu, X. Yu, and K. Sui, “Long non-coding RNA KCNQ1OT1 Promotes the Progression of Gastric Cancer via the miR-145-5p/ARF6 Axis,” The Journal of Gene Medicine 23, no. 5 (2021): e3330, https://doi.org/10.1002/jgm.3330.
The above article, published online on 8 March 2021 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Jiang Fan; and John Wiley & Sons Ltd. The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Several flaws and inconsistencies between results presented and experimental methods described were found. Specifically, multiple image elements were found to have been published elsewhere in a different scientific context. Furthermore, the article presents results from multiple non-verifiable/unknown cell lines: BSG823, BSG803, BGC803, and GSE1. Accordingly, the conclusions of this article are considered invalid by the editors. The authors have been informed of the decision of retraction but unavailable for a final confirmation.
Lovastatin, a type of statin usually considered as a lipid-lowering drug that lowers blood cholesterol and low-density lipoprotein cholesterol levels, has been rediscovered to have anticancer activity. Fewer studies exist regarding the effect of lovastatin on esophageal squamous cell carcinoma (ESCC).
Here, we report that lovastatin shows anticancer effect on ESCC By affecting the mitochondrial autophagy pathway. Moreover, based on proteomics and computer molecular simulations found that RAB38 and RAB27A may be a target of lovastatin.
We observed that autophagy of mitochondria is inhibited by lovastatin, affecting esophageal squamous cell proliferation. There is a possible link between the expression of RAB38, RAB27A and immune cell invasion in esophageal cancer.
These results demonstrate the huge potential of lovastatin as an RAB38, RAB27A inhibitor in esophageal cancer chemotherapy and chemoprevention.
To date, 3,900 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical activity from trial databases, official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our March 2023 update, we have entries on 3,900 trials undertaken in 46 countries. We have analyzed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and which genes have been transferred. Details of the analyses presented, and our searchable database are on The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at https://a873679.fmphost.com/fmi/webd/GTCT. We also provide an overview of the progress being made around the world, and discuss key trends since the previous review, namely the unprecedented increase in gene therapy clinical trial activity, including the implementation of genome editing technology with the potential to transform the field moving forward.
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