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The majority of esophageal squamous dysplasia (ESD) patients progress slowly, while a subset of patients can undergo recurrence rapidly or progress to invasive cancer even after proper treatment. However, the molecular mechanisms underlying these clinical observations are still largely unknown.

Cyclin B1 is an essential cyclin-dependent protein that involves in the G2/M transition. Multiple studies report that cyclin B1 is upregulated in cancers and promotes cancer progression. However, the mechanism of cyclin B1 upregulation remains unclear. Here we report that the 5′UTR of cyclin B1 mRNA contains an internal ribosome entry site (IRES) by using a bicistronic fluorescent reporter. We show that IRES can initiate the translation of cyclin B1, and the IRES-mediated translation is further activated under cell stress. Interacting trans-acting factors (ITAFs) are required by most IRES to initiate the translation. We find that PTBP1 promotes the IRES-mediated translation of cyclin B1 by binding to the 5′UTR of cyclin B1. On top of that, PTBP1 promotes the malignancy of ESCC cells. Our data suggest that the IRES-mediated translation of cyclin B1 plays an essential role in the cyclin B1 upregulation in cancers.

Background: The concept of gene fusion describes the process of fusing two genes into one, which is closely linked to tumour occurrence and development and may even be the direct cause of some tumours. Due to their tumour‐specific expression and ability to drive tumour occurrence and development, there is great potential for fusion genes to be used as diagnostic markers and targets for specific types of tumours. Main body: Although many fusion genes have been detected so far, they mainly focus on a small number of highly recurrent fusion genes detected in patients' tumours. There are few studies on the functional mechanism and clinical relevance of rare gene fusions. Our review discusses the generation mechanisms, detection methods, biological functions, and mechanisms of action of fusion genes. Additionally, we discuss the clinical significance of fusion gene detection in some tumour types. Conclusion: The function mechanism research of rare gene fusion is very necessary, and more functions of fusion genes independent of unfused/normal genes can be explored in future studies. There is still a long way to go in implementing precision tumour therapy targeting gene fusion. [ABSTRACT FROM AUTHOR]

The primary challenge in treating esophageal squamous cell carcinoma (ESCC) is resistance to chemotherapy. Cancer stem cell (CSC) is the root cause of tumor drug resistance. Therefore, targeting CSCs has been considered promising therapeutic strategy for tumor treatment. Here, we report that circMALAT1 was significantly upregulated in ESCC CSC‐like cells and primary tumors from ESCC patients. Clinically, there was a positive correlation between circMALAT1 expression and ESCC stage and lymph node metastasis, as well as poor prognosis for ESCC patients. In vitro and in vivo functional studies revealed that circMALAT1 promoted CSC‐like cells expansion, tumor growth, lung metastasis and drug resistance of ESCC. Mechanistically, circMALAT1 directly interacted with CSC‐functional protein Musashi RNA Binding Protein 2 (MSI2). CircMALAT1 inhibited MSI2 ubiquitination by preventing it from interacting with β‐transducin repeat containing protein (BTRC) E3 ubiquitin ligase. Also, circMALAT1 knockdown inhibited the expression of MSI2‐regulating CSC‐markers c‐Myc in ESCC. Collectively, circMALAT1 modulated the ubiquitination and degradation of the MSI2 protein signaling with ESCC CSCs and accelerated malignant progression of ESCC. CircMALAT1 has the potential to serve as a biomarker for drug resistance and as a target for therapy in CSCs within ESCC. [ABSTRACT FROM AUTHOR]

Multifocal esophageal squamous cell carcinomas (ESCCs) can be diagnosed as of multicentric origin (MO) or intramural metastasis (IMM). We aimed here to accurately discriminate MO from IMM and explore the tumor immune microenvironment of multifocal ESCCs. Multifocal ESCCs were identified in 333 ESCC patients, and in 145 patients discrimination between MO and IMM was not possible by histopathological examination. Of the 145 patients, tissues of 14 were analyzed by whole‐exome sequencing (WES) of 71 different tumor regions, and MO, IMM, and MO/IMM mixed groups were identified in three, ten, and one cases, respectively, based on the similarity of genomic architecture between or among different tumors from one patient. Further phylogenetic analyses revealed complex clonal evolution patterns in IMM cases, and tumor cells disseminated from the primary tumors to IMM tumors were independent of lymph node metastasis. The NanoString‐based assay showed that immune cell infiltrates were significantly enriched, and that the immune and proliferation pathways were more activated, in large tumors than in small ones in MO but not IMM cases. Similarly, PD‐L1 expression and the density of paratumoral CD8+ T cells were higher in large tumors than in small tumors in MO. Taken together, through analysis of the genomic and immune landscapes, our study has comprehensively characterized the heterogeneity and clonal relationship of multifocal ESCCs, which may be helpful in distinguishing MO from IMM, and for interpreting the immunotherapy responses for multifocal ESCC patients. © 2022 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

We propose a label-free method to analyze bodily fluids based on surface-enhanced Raman scattering (SERS) with large laser spot-swift mapping and involving the electrochemistry preparation of silver nanoparticle substrates. This method can analyze the overall properties of multicomponent liquid and identify the low-concentration components. A large laser spot formed by a scanning galvanometer is used to obtain an average spectrum from different samples, whereas swift mapping detects low-concentration components such as tumor biomarkers. The silver nanoparticle substrates used exhibit strong SERS activity and wettability, improving adsorption and avoiding sample cluster formation. We applied this method to serum-based cancer diagnosis. Accuracy of the large spot method was tested by comparison with mass spectrometry results, whereas sensitivity of swift mapping was verified by detection of carcinoembryonic antigen in early colorectal cancer serum. Several cancer-related Raman peaks may be used as predictors, like a peak at 710 cm–1 which may represent an increase of circulating tumor DNA and metabolism disorder. We assess the potential application of this method for pan-cancer detection and staging. This method has advantage in sensitivity and reproducibility and is expected to play an important role in the analysis of complex component liquids that experience subtle changes that form on mechanism. [ABSTRACT FROM AUTHOR]

Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target., Introduction The centrosome is a small cytoplasmic nonmembranous organelle involved in the nucleation and organization of microtubules and critical for proper cell cycle progression. It establishes polarity and orientation of [...]