RESUMO
ARID3A is upregulated in colorectal cancer and can promote the proliferation and metastasis of cancer cells. However, patients with higher level of ARID3A have a better prognosis. This study aimed to uncover the mechanism by which ARID3A benefits the prognosis of colon cancer. Our results indicated that ARID3A upregulation enhanced the chemosensitivity of colon cancer cells to 5-fluorouracil (5-FU), whereas ARID3A downregulation inhibited the chemosensitivity of colon cancer cells to 5-FU. Through database analysis, we found that AKR1C3, a drug resistance-related gene, was the target of ARID3A. Moreover, AKR1C3 was downregulated in colon cancer tissues compared to normal tissues. Next, we assessed the interaction between AKR1C3 and ARID3A, and found that ARID3A inhibited the transcription of AKR1C3, leading to the downregulation of AKR1C3 in colon cancer cells. We also verified that AKR1C3 inhibited the chemosensitivity of colon cancer cells to 5-FU. Moreover, patients with higher ratio of ARID3A to AKR1C3 had a better prognosis. This study suggested that ARID3A promoted chemosensitivity of colon cancer cells by inhibiting AKR1C3 in colon cancer. The ratio of ARID3A to AKR1C3 is a good marker to predict the prognosis of colon cancer patients.
Assuntos
Membro C3 da Família 1 de alfa-Ceto Redutase , Neoplasias do Colo , Proteínas de Ligação a DNA , Fatores de Transcrição , Membro C3 da Família 1 de alfa-Ceto Redutase/antagonistas & inibidores , Membro C3 da Família 1 de alfa-Ceto Redutase/genética , Membro C3 da Família 1 de alfa-Ceto Redutase/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/farmacologia , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para CimaRESUMO
KEY MESSAGE: Pm57, a novel resistant gene against powdery mildew, was transferred into common wheat from Ae. searsi and further mapped to 2S s #1L at an interval of FL0.75 to FL0.87. Powdery mildew, caused by the fungus Blumeria graminis f. sp. tritici, is one of the most severe foliar diseases of wheat causing reduction in grain yield and quality. Host plant resistance is the most effective and environmentally safe approach to control this disease. Tests of a set of Chinese Spring-Ae. searsii (SsSs, 2n = 2x = 14) Feldman & Kislev ex K. Hammer disomic addition lines with a mixed isolate of the powdery mildew fungus identified a novel resistance gene(s), designed as Pm57, which was located on chromosome 2Ss#1. Here, we report the development of ten wheat-Ae. searsii recombinants. The wheat chromosomes involved in five of these recombinants were identified by FISH and SSR marker analysis and three of them were resistant to powdery mildew. Pm57 was further mapped to the long arm of chromosome 2Ss#1 at a fraction length interval of FL 0.75 to FL 0.87. The recombinant stocks T2BS.2BL-2Ss#1L 89-346 (TA5108) with distal 2Ss#1L segments of 28% and 89(5)69 (TA5109) with 33% may be useful in wheat improvement. The PCR marker X2L4g9p4/HaeIII was validated to specifically identify the Ae. searsii 2Ss#1L segment harboring Pm57 in T2BS.2BL-2Ss#1L against 16 wheat varieties and advanced breeding lines, and the development of more user-friendly KASP markers is underway.