Rectal neuroendocrine tumor with uncommon metastatic spread:A case report and review of literature

Neuroendocrine tumors of the gastrointestinal tract are rare neoplasms. Rectal neuroendocrine tumors consist approximately the 5%-14% of all neuroendocrine neoplasms in Europe. These tumors are diagnosed in relatively young patients,with a mean age at diagnosis of 56 years. Distant metastases from rectal neuroendocrine tumors are not very common. Herein we describe a case of a rectal neuroendocrine tumor which metastasized to the lung,mediastinum and orbit. This case underscores the importance of early identification and optimal management to improve patient's prognosis. Therefore,the clinical significance of this case is the necessity of physicians' awareness and education regarding neuroendocrine tumors' diagnosis and management.

Genetic polymorphisms of interleukin 1β gene and sporadic pancreatic neuroendocrine tumors susceptibility

AIM.:To evaluate the association between the interleukin 1β(IL-1β) polymorphisms and the pancreatic neuroendocrine tumor(pN ET) development.METHODS.:A case-control study was conducted analyzing IL-1β polymorphisms using germline DNA collected in a population-based case-control study of pancreatic cancer(51 pN ET cases,85 pancreatic ductal adenocarcinoma cases,19 intraductal papillary mucinous neoplasm and 98 healthy controls).RESULTS.:The distribution of genotypes for the-511C/T polymorphism in the pN ET patient groups showed significant difference compared to the control group.It is known that the carriers of the IL-1β-511 T allele have increased concentrations of IL-1β.The-511 CT and TT high-expression genotypes were over-represented in pN ET patients.CONCLUSION.:The findings of this study suggested a possible role of IL-1β-511 C/T genotypes in the pathogenesis of pN ETs since the presence of the IL-1β-511 CT and TT genotypes and the T allele was associated with an increased risk of pN ET only.

FBXW7βloss-of-function enhances FASN-mediated lipogenesis and promotes colorectal cancer growth

Continuous de novo fatty acid synthesis is required for the biosynthetic demands of tumor.FBXW7 is a highly mutated gene in CRC,but its biological functions in cancer are not fully characterized.Here,we report that FBXW7β,a FBXW7 isoform located in the cytoplasm and frequently mutated in CRC,is an E3 ligase of fatty acid synthase(FASN).Cancer-specific FBXW7βmutations that could not degrade FASN can lead to sustained lipogenesis in CRC.COP9 signalosome subunit 6(CSN6),an oncogenic marker of CRC,increases lipogenesis via interacting with and stabilizing FASN.Mechanistic studies show that CSN6 associates with both FBXW7βand FASN,and antagonizes FBXW7β’s activity by enhancing FBXW7βautoubiquitination and degradation,which in turn prevents FBXW7β-mediated FASN ubiquitination and degradation,thereby regulating lipogenesis positively.Both CSN6 and FASN are positively correlated in CRC,and CSN6-FASN axis,regulated by EGF,is responsible for poor prognosis of CRC.The EGF-CSN6-FASN axis promotes tumor growth and implies a treatment strategy of combination of orlistat and cetuximab.Patient-derived xenograft experiments prove the effectiveness of employing orlistat and cetuximab combination in suppressing tumor growth for CSN6/FASN-high CRC.Thus,CSN6-FASN axis reprograms lipogenesis to promote tumor growth and is a target for cancer intervening strategy in CRC.

Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer

MTUS1 （microtubule-associated tumor suppressor 1） has been identified that can function as a tumor sup- pressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b （miR-19a/b） promote prolifer- ation and migration of lung cancer cells by targeting MTUS1. First, MTUS1 was proved to function as a tumor suppressor in lung cancer and was linked to cell prolif- eration and migration promotion. Second, an inverse correlation between miR-19a/b expression and MTUS1 mRNA/protein expression was noted in human lung cancer tissues. Third, MTUS1 was appraised as a direct target of miR-19a/b by bioinformatics analysis. Fourth, direct MTUS1 regulation by miR-19a/b in lung cancer cells was experimentally affirmed by cell transfection assay and luciferase reporter assay. Finally, miR-19a/b were shown to cooperatively repress MTUS1 expression and synergistically regulate MTUS1 expression to pro- mote lung cancer cell proliferation and migration. In conclusion, our findings have provided the first cluesregarding the roles of miR-19a/b, which appear to func- tion as oncomirs in lung cancer by downregulating MTUSI.