GALNT10 promotes the proliferation and metastatic ability of gastric cancer and reduces 5-fluorouracil sensitivity by activating HOXD13.

Abstract

To investigate the expression and potential mechanism of GALNT10 in gastric cancer (GC). A total of 60 cases of GC tissues, as well as normal tissues were collected. The total RNA of GC specimens and cells were extracted by TRIzol method and the level of GALNT10 was examined by quantitative real-time polymerase chain reaction (qRT-PCR). In addition, the relationship between GALNT10 and clinical parameters and prognosis of GC patients was analyzed. Subsequently, Lentivirus was used to construct GALNT10 knockdown GC cell lines, and cell counting kit-8 (CCK-8) and transwell assays were applied to analyze the influence of GALNT10 on GC cell function. Bioinformatics and Luciferase assay was used to evaluate the relationship between GALNT10 and HOXD13. Furthermore, 5-fluorouracil (5-Fu)-resistant cells were used to detect the relationship between GALNT10 and 5-Fu sensitivity of GC cells. qRT-PCR results revealed that GALNT10 level was markedly increased in tissues, as well as cell lines of GC. Statistical analysis suggested that GALNT10 expression was in close relation with the incidence of lymph node and distant metastasis along with poor prognosis in GC patients, but not with other indicators. CCK-8 and transwell migration experiment results indicated that GALNT10 silencing can inhibit the proliferative and migration ability of GC cells. Western blot results displayed that the HOXD13 level was remarkably decreased after GALNT10 knocking down. In addition, Luciferase gene assay indicated that GALNT10 could bind to HOXD13. Further rescue experiments showed that HOXD13overexpression can synergistically reverse the inhibitory effect of GALNT10 knockdown on GC cell proliferative and migration ability, which further demonstrated that GALNT10 could promote GC cell metastasis ability and reduce the sensitivity to 5-Fu by regulating HOXD13. GALNT10 could regulate the proliferative and migration ability of GC cells and reduce the sensitivity to 5-Fu by enhancing the expression of HOXD13. Therefore, GALNT10 was expected to be a new therapeutic target for diagnosis of 5-fluorouracil resistance in GC.