Published online Jul 7, 2020. doi: 10.3748/wjg.v26.i25.3586
Peer-review started: February 3, 2020
First decision: March 24, 2020
Revised: March 26, 2020
Accepted: May 26, 2020
Article in press: May 26, 2020
Published online: July 7, 2020
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid tumors. Identification of diagnostic and therapeutic biomarkers for PDAC is urgently needed. Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) has been linked to the progression of various human cancers. Nevertheless, the function and role of TBL1XR1 in pancreatic cancers are unclear.
To elucidate the function and potential mechanism of TBL1XR1 in the development of PDAC.
Ninety patients with histologically-confirmed PDAC were included in this study. PDAC tumor samples and cell lines were used to determine the expression of TBL1XR1. CCK-8 assays and colony formation assays were carried out to assess PDAC cell viability. Flow cytometry was performed to measure the changes in the cell cycle and cell apoptosis. Changes in related protein expression were measured by western blot analysis. Animal analysis was conducted to confirm the impact of TBL1XR1 in vivo.
Patients with TBL1XR1-positive tumors had worse overall survival than those with TBL1XR1-negative tumors. Moreover, we found that TBL1XR1 strongly promoted PDAC cell proliferation and inhibited PDAC cell apoptosis. Moreover, knockdown of TBL1XR1 induced G0/G1 phase arrest. In vivo animal studies confirmed that TBL1XR1 accelerated tumor cell growth. The results of western blot analysis showed that TBL1XR1 might play a key role in regulating PDAC cell proliferation and apoptosis via the PI3K/AKT pathway.
TBL1XR1 promoted PDAC cell progression and might be an effective diagnostic and therapeutic marker for pancreatic cancer.
Core tip: Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) has been linked to the progression of various human cancers. However, the function and role of TBL1XR1 in pancreatic cancers are unclear. Elucidation of the effect and potential molecular mechanism of TBL1XR1 in pancreatic cancer is important. This study showed that TBL1XR1 promoted pancreatic ductal adenocarcinoma (PDAC) cell proliferation, inhibited PDAC cell apoptosis and might regulate PDAC cell proliferation and apoptosis by the phosphatidylinositol 3-kinase/protein kinase B pathway. Therefore, TBL1XR1 might be a promising therapeutic marker for patients with advanced PDAC.