RNA-binding protein CELF1 enhances cell migration, invasion, and chemoresistance by targeting ETS2 in colorectal cancer.

Colorectal cancer (CRC) is often diagnosed at later stages after it has metastasized to other organs. The development of chemoresistance also contributes to a poor prognosis. Therefore, an increased understanding of the metastatic properties of CRC and chemoresistance could improve patient survival. CUGBP elav-like family member 1 (CELF1) is an RNA-binding protein, which is overexpressed in many human malignant tumors. However, the influence of CELF1 in CRC is unclear. V-ets erythroblastosis virus E26 oncogene homologue 2 (ETS2) is an evolutionarily conserved proto-oncogene known to be overexpressed in a variety of human cancers including CRC. In thespresent tudy, we investigated the association between CELF1 and ETS2 in CRC tumorigenesis and oxaliplatin (L-OHP) resistance. We found a positive correlation between the elevated expression of CELF1 and ETS2 in human CRC tissues. Overexpression of CELF1 increased CRC cell proliferation, migration, and invasion in vitro and in a xenograft tumor growth model in vivo, and induced resistance to L-OHP. In contrast, CELF1 knockdown improved the response of CRC cells to L-OHP. Overexpression of ETS2 increased the malignant behavior of CRC cells (growth, migration, and invasion) and L-OHP resistance in vitro. Moreover, L-OHP resistance induced by CELF1 overexpression was reversed by ETS2 knockdown. The results of luciferase reporter and ribonucleoprotein immunoprecipitation assays indicated that CELF1 up-regulates ETS2 by binding to its 3'-UTR. Taken together, our findings have identified that CELF1 regulates ETS2 in a mechanism that results in CRC tumorigenesis and L-OHP resistance, and CELF1 may be a promising target for overcoming chemoresistance in CRC.

Radical excision versus local resection for primary rectal gastrointestinal stromal tumors. Cohort Study.

BACKGROUND: Rectal gastrointestinal stromal tumor (GIST) is a rare digestive disease that originates in mesenchymal tissues and has malignant tendencies. At present, no standard treatment has been developed, and surgical approaches and the resection scope for rectal GISTs are controversial. METHODS: The clinical, surgical, pathological and prognosis data of patients with primary rectal GIST in our center from January 2008 to January 2019 were retrospectively collected. The patients were divided into the radical excision (RE) and local resection (LR) groups. RESULTS: A total of 537 GIST cases were collected, and 64 patients with primary rectal GIST were included in this study, including 25 cases in the RE group and 39 cases in the LR group. Tumor size (p = 0.013), distance from the anus (p = 0.038), National Institutes of Health (NIH) criteria (p = 0.001), preoperative adjuvant therapy (p = 0.016), postoperative adjuvant therapy (p = 0.028), blood loss (p = 0.048), operative time (p = 0.020) and the duration of hospitalization (p = 0.021) were statistically different between these 2 groups. The mean overall follow-up time was 46 months (range, 1-122 months). Disease recurrence was observed in 12 patients. No statistical differences were observed in 5-year disease-free survival (DFS) (93.3% vs 92.6%, p = 0.952) or overall survival (OS) (90.0% vs 91.6%, p = 0.832) between the RE group and the LR group. CONCLUSION: Our study showed that LR has a similar prognosis to that of RE with respect to DFS and OS. For appropriate cases, LR has the advantages of a short operative time, less bleeding, and a quick recovery. Especially when combined with neoadjuvant therapy, LR can also achieve better perioperative efficacy. Therefore, LR is an effective method for resection of rectal GISTs and warrants clinical endorsement.