Recently, Prof. Rufu Chen’s research group of our Pancreatic Center reported a research on the molecular mechanism that LncRNA-PLACT1 sustains activation of NF-κB pathway through a positive feedback loop with IκBα/E2F1 axis in pancreatic cancer. The relevant research results were published in late February 2020 in the journal Molecular Cancer (IF=10.679, IF=15.41 in 2020) entitled “lncRNA-PLACT1 sustains activation of NF-κB pathway through a positive feedback loop with IκBα/E2F1 axis in pancreatic cancer”, which is another fundamental research innovation achievement related to pancreatic cancer published in a high-level journal by the Chinese scholars of pancreatic surgery in recent years. In addition, last October, Prof. Rufu Chen published an article in J Clin Invest (Impact Factor 12.282) in collaboration with Prof. Tianxin Lin and Prof. Jian Huang of Sun Yat-sen Memorial Hospital affiliated to Sun Yat-Sen University, introducing a new mechanism of tumor cell-secreted exosome-mediated lymphangiogenesis promoting lymph node metastasis of tumor cells.
The activation of NF-κB signaling pathway is regarded as the dominant process that correlates with tumorigenesis. Recently, increasing evidence shows that long noncoding RNAs (lncRNAs) play crucial roles in sustaining the NF-κB signaling pathway. However, the underlying mechanisms have not been elucidated yet. Prof. Rufu Chen’s research team analyzed the expression and clinical features of PLACT1 in a 166-case cohort of PDAC by qRT-PCR and in situ hybridization. The functional role of PLACT1 was evaluated by both in vitro and in vivo experiments. Chromatin isolation by RNA purification assays was utilized to examine the interaction of PLACT1 with IκBα promoter.
The research group identified a novel lncRNA-PLACT1, which was significantly upregulated in tumor tissues and correlated with progression and poor survival in PDAC patients. Moreover, PLACT1 promoted the proliferation and invasion of PDAC cells in vitro. Consistently, PLACT1 overexpression fostered the progression of PDAC both in orthotopic and lung metastasis mice models. Mechanistically, PLACT1 suppressed IκBα expression by recruiting hnRNPA1 to IκBα promoter, which led to increased H3K27me3 that decreased the transcriptional level of IκBα. Furthermore, E2F1-mediated overexpression of PLACT1 modulated the progression of PDAC by sustained activation of NF-κB signaling pathway through forming a positive feedback loop with IκBα. Importantly, administration of the NF-κB signaling pathway inhibitor significantly suppressed PLACT1-induced sustained activation of NF-κB signaling pathway, leading to reduced tumorigenesis in vivo. In summary, the findings suggest that PLACT1 provides a novel epigenetic mechanism involved in constitutive activation of NF-κB signaling pathway and may represent a new therapeutic target of PDAC.
Pancreatic surgery is a very challenging specialty and regarded as the “pearl in the crown” of abdominal surgery. Since the establishment of the Pancreatic Center (South China Diagnosis and Treatment Center for Pancreatic Minimally Invasive Surgery), clinical and scientific researches have been strengthened concurrently under the leadership of Prof. Rufu Chen, vice president of Guangdong Academy of Medical Sciences, director of General Surgery Department of Guangdong Provincial People's Hospital and director of the Pancreatic Center. The Center continues to innovate and move forward based on the “Summit Plan” of the hospital and gain innumerable great achievements.The discipline has developed rapidly in the field of pancreatology, and the total number of patients receiving diagnosis and treatment at the Pancreatic Center has increased rapidly. The academic influence at home and abroad has been climbing.
In 2019, Prof. Rufu Chen successfully completed 170 cases of total laparoscopic pancreaticoduodenectomy; the department successfully held seven national live demonstrations of minimally invasive pancreatic surgery, with the total number of online and offline viewers exceeding 30,000; successfully held the 13th China Pancreatic Cancer Congress, during which the Pancreatic Center took the lead in establishing the South China Pancreatic Minimally Invasive Alliance as the president unit; actively interacted with renowned experts in the field of pancreatology from the Johns Hopkins Hospital of the United States, Singapore General Hospital, and Changi General Hospital of Singapore; published a number of high-quality original clinical and fundamental research results, and has made academic speeches at the Asia-Pacific and Whole American Hepatobiliary and Pancreatic Annual Conferences. In addition, as the president of Guangdong Provincial Association of Primary Medicine, Prof. Rufu Chen has actively helped the surgical development and construction of primary hospitals.
Being internationalized, specialized and professionalized, the Pancreatic Center is dedicated to realize the precise diagnosis and treatment based on the multidisciplinary diagnosis and treatment of pancreatic cancer. In line with the concept of serving patients, the Center will continue to maintain its medical style of “working hard to overcome difficulties and bravely scaling new heights”. Driven by the two engines of clinical technology and scientific research, the Center serves South China and caters to the whole nation by providing first-class diagnosis and treatment services for patients with all kinds of pancreatic diseases.
