LINC01503 promotes progression of epithelial ovarian cancer through the miR-342-3p/IGF2R axis
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Abstract:
To investigate the expression level, biological function and possible mechanism of LINC01503 in epithelial ovarian cancer (EOC). Methods: A total of 85 pairs of tumor tissues and fallopian tube tissues from EOC patients who underwent ovarian tumor reduction surgery in the Department of Gynecology, the Fourth Hospital of Hebei Medical University from May 2015 to May 2016 were collected. Human EOC cells A2780, SKOV3, OVCAR3 and OV90 and normal human ovarian epithelial cells IOSE80 were routinely cultured, and si-LINC01503, si-NC, and miR-342-3p mimic, miR mimic NC were transfected into SKOV3 and A2780 cells, respectively, and recorded as si-LINC01503 group, si-NC group, miR-342-3p mimic group and miR mimic NC group. qPCR was used to detect the expression level of LINC01503 in EOC tissues and cells, and Kaplan-Meier method was used to analyze the correlation between the expression of LINC01503 and the survival of EOC patients. Dual-luciferase reporter gene assay was used to verify the targeting relationship among melecules associated with LINC01503/miR-342-3p/IGF2R (insulin like growth factor 2 receptor) axis. The effects of LINC01503 knockdown and miR-342-3p over-expression on proliferation, migration and invasion of EOC A2780 and SKOV3 cells were detected by plate cloning assay, scratch wound healing assay and Transwell assay, respectively. The effect of LINC01503/miR-342-3p pathway on IGF2R protein expression was detected by WB method in SKOV3 and A2780 cells. A nude mouse model of A2780 cell transplanted tumor was established to observe the effect of LINC01503 on the growth of transplanted tumor. Results: The expression levels of LINC01503 in EOC tissues and cells were significantly higher than that in fallopian tube tissues and IOSE80 cells (all P<0.01). Kaplan-Meier survival analysis showed that compared with the low LINC01503 expression group, patients in the high LINC01503 expression group had significantly shorter PFS and OS after surgery (all P<0.01). Knockdown of LINC01503 and over-expression of miR-342-3p could inhibit proliferation, migration, and invasion of EOC cells (all P<0.01). WB results showed that knockdown of LINC01503 down-regulated the expression of IGF2R (P<0.01), which could be saved by transfection of miR-342-3p inhibitor (P<0.01). LINC01503 knockdown could inhibit the growth of A2780 cell transplanted tumors in vivo (P<0.01). Conclusion: LINC01503 is highly expressed in EOC tissues and cells, and it is significantly related to the poor prognosis of EOC patients. LINC01503 promotes the development of EOC possibly by upregulating IGF2R via sponging miR-342-3p.