A laparoscopic pancreaticoduodenectomy for pancreatic adenocarcinoma in a patient with situs inversus totalis.

Situs inversus totalis (SIT) is a congenital disorder in which the thoracic and abdominal viscera organs are mirrored from their normal anatomical position. Thus, the presence of any cancerous mass in one of the visceral organs of patients with SIT represents a great challenge due to the anatomical variation. We report a 52-year-old male with SIT who presented with obstructive jaundice and pancreatic-head mass. After preoperative examinations, it was decided to perform a laparoscopic pancreaticoduodenectomy. In this case, we aim to demonstrate the diagnosis and management of pancreatic cancer in an SIT patient, in addition to presenting the advantages and difficulties of laparoscopic surgery in this case.

PLAGL2 and POFUT1 are regulated by an evolutionarily conserved bidirectional promoter and are collaboratively involved in colorectal cancer by maintaining stemness.

BACKGROUND: Our previous study revealed that PLAGL2 or POFUT1 can promote tumorigenesis and maintain significant positive correlations in colorectal cancer (CRC). However, the mechanism leading to the co-expression and the underlying functional and biological implications remain unclear. METHODS: Clinical tumor tissues and TCGA dataset were utilized to analyze the co-expression of PLAGL2 and POFUT1. Luciferase reporter assays, specially made bidirectional promoter vectors and ectopic expression of 3'UTR were employed to study the mechanisms of co-expression. In vitro and in vivo assays were performed to further confirm the oncogenic function of both. The sphere formation assay, immunofluorescence, Western blot and qRT-PCR were performed to investigate the effect of both genes in colorectal cancer stem cells (CSCs). FINDINGS: PLAGL2 and POFUT1 maintained co-expression in CRC (r = 0.91, p < .0001). An evolutionarily conserved bidirectional promoter, rather than post-transcriptional regulation by competing endogenous RNAs, caused the co-expression of PLAGL2 and POFUT1 in CRC. The bidirectional gene pair PLAGL2/POFUT1 was subverted in CRC and acted synergistically to promote colorectal tumorigenesis by maintaining stemness of colorectal cancer stem cells through the Wnt and Notch pathways. Finally, PLAGL2 and POFUT1 share transcription factor binding sites, and introducing mutations into promoter regions with shared transcription regulatory elements led to a decrease in the PLAGL2/POFUT1 promoter activity in both directions. INTERPRETATION: Our team identified for the first time a bidirectional promoter pair oncogene, PLAGL2-POFUT1, in CRC. The two genes synergistically promote the progression of CRC and affect the characteristics of CSCs, which can offer promising intervention targets for clinicians and researchers. FUND: National Nature Science Foundation of China, the Hunan province projects of Postgraduate Independent Exploration and Innovation of Central South University.

Overexpressed PLAGL2 transcriptionally activates Wnt6 and promotes cancer development in colorectal cancer.

Researchers hold the view that PLAGL2 is overexpressed in many malignancies and that it can promote tumor proliferation, migration, invasion and self­renewal; however, there is no evidence revealing a relationship between PLAGL2 and colorectal cancer (CRC). In the present study, genes that are overexpressed in CRC were screened using the COSMIC database and GEPIA database and the expression of PLAGL2 in carcinoma tissues and pericarcinomatous tissues was detected by RT­qPCR and western blot assays. A Cell Counting Kit­8 assay, a cell cycle analysis experiment and a xenograft model were used to explore the influence of PLAGL2 on CRC after knocking down PLAGL2 expression in HCT116 and SW480 cells. Using ChIP assays and Dual­Luciferase Reporter assays, the promoter regions to which PLAGL2 binds were discovered. It was observed that PLAGL2 was overexpressed in colorectal cancer and that it influenced the colorectal cancer cell cycle and promoted colorectal cancer proliferation in vivo and in vitro. The expression of some genes in the Wnt/ß­catenin pathway, were downregulated after knocking down the expression of PLAGL2; Wnt6 was altered the most. PLAGL2 could bind to the promoter region of Wnt6 and promote its expression. These results indicated that PLAGL2 was overexpressed in CRC as a proto­oncogene and that it could active the Wnt/ß­catenin pathway as a transcription factor by binding with the promoter region of Wnt6. PALGL2 was revealed to play an important role in colorectal cancer and may be a new therapeutic target for targeted medicine.

POFUT1 promotes colorectal cancer development through the activation of Notch1 signaling.

Copy number variations (CNVs) are key drivers of colorectal cancer (CRC). Our previous studies revealed that protein O-fucosyltransferase 1 (POFUT1) overexpression is driven by CNVs during CRC development. The potential role and underlying mechanisms of POFUT1 in CRC were not investigated. In this study, we analyzed the expression of POFUT1 in CRC from cosmic and TCGA databases and confirmed that POFUT1 is highly expressed in CRC. We used well characterized CRC cell lines, including SW620 and HCT116 to establish a model POFUT1 knockdown cell line. Using these cells, we investigated the role of POFUT1 in CRC. Our data revealed that silencing POFUT1 in CRC cells inhibits cell proliferation, decreases cell invasion and migration, arrests cell cycle progression, and stimulates CRC cell apoptosis in vitro. We further demonstrate that POFUT1 silencing dramatically suppresses CRC tumor growth and transplantation in vivo. We additionally reveal new mechanistic insights into the role of POFUT1 during CRC, through demonstrating that POFUT1 silencing inhibits Notch1 signaling. Taken together, our findings demonstrate that POFUT1 is a tumor activating gene during CRC development, which positively regulates CRC tumor progression through activating Notch1.

Studying the mechanism of PLAGL2 overexpression and its carcinogenic characteristics based on 3'-untranslated region in colorectal cancer.

Pleomorphic adenoma gene like-2 (PLAGL2) is a zinc finger protein transcription factor, which is upregulated and serves an oncogenic function in multiple human malignancies, including colorectal cancer (CRC). First, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of PLAGL2 in CRC tissues and normal tissues. Then, bioinformatics analysis, RT-qPCR, western blotting, luciferase reporter assays and RNA-binding protein immunoprecipitation assays were performed to explore whether the underlying mechanisms, including copy number variation (CNV), microRNAs (miRNAs/miRs) and RNA-binding proteins (RBPs) led to the abnormal expression of PLAGL2. Finally, cell counting kit-8 assays, Transwell assays and xenograft models were used to detect carcinogenesis-associated characteristics based on the 3'-untranslated region (3'-UTR) of PLAGL2. In the present study, PLAGL2 was revealed to be upregulated in CRC tissues compared with normal CRC tissues. CNV was one of the causes leading to the upregulation of PLAGL2. miRNA, including downregulated miR-486-5p, and RBPs, including upregulated human antigen R (HuR), were other key underlying causes. In addition, PLAGL2 3'-UTR was revealed to promote the progression of CRC in vitro and in vivo, and to regulate the expression of C-MYC and CD44. To conclude, these results suggested that high expression of PLAGL2 in CRC was associated with CNV, miR-486-5p and HuR expression, whose 3'-UTR may promote colon carcinogenesis and serve as a novel potential biomarker for CRC therapies.

Comprehensive bioinformatics analysis of the characterization and determination underlying mechanisms of over-expression and co-expression of genes residing on 20q in colorectal cancer.

The Long arm of chromosome 20 (20q) is closely related to the development of colorectal cancer, so identifying the expression profile of genes on 20q through a comprehensive overview is indispensable. In this article, preliminar experimental data, several available databases and bioinformatics tools such as the Cancer Genome Atlas, the Encyclopedia of DNA Elements, the JASPAR database and starBase were combined to analyze the correlation between genes and chromosomal aberrations, microRNA and transcription factors, as well as to explore the expression feature and potential regulative mechanism. The results showed that the most frequently unregulated genes in colorectal cancer arelocated on chromosome 20q, present a significant CNA-mRNA correlation.Furthermore, the genes with mRNA overexpression showed co-expression features and tended to be clustered within the same genomic neighborhoods. Then, several genes were selected to carry out further analysis and demonstrated that shared transcription factors, a conserved bidirectional promoter, and competition for a limited pool of microRNAin the 3'UTR of mRNA may be the underlying mechanisms behind the co-expression of physically adjacent genes.Finally, the databases, Lentivirus shRNA, and qPCR were used to find that these adjacent genes with co-expression cooperatively participated in the same biological pathways associated with the pathogenesis and development of colorectal cancer.