It is known that LINC01018 and CDK6 are associated with the occurrence, progression and recurrence of malignant tumor. Our preliminary data showed that the expression of LINC01018 was down-regulated and that of CDK6 was up-regulated, which were related with the malignancy grade. Bioinformatics suggested that E2F1 binding site exist in the CDK6 promoter region, and LINC01018 might interact with E2F1. Thus we speculate that the expression of LINC01018 in malignant tumor is decreased. The interaction between LINC01018 and E2F1 activates E2F1, promotes the transcription activation of CDK6, and affects tumor proliferation, invasion and metastasis. All these are expected to reveal the effect and mechanisms of LINC01018 in the development and regulation of malignant tumor, and provide new ideas and evidences for its treatment.

BACKGROUND: The role of sex hormones and their receptors has drawn much attention in the process of cartilage regeneration. This study aimed to investigate the effect of androgen receptor (AR) on the chondrogenic ability of articular chondrocytes and the related mechanism. METHODS: Articular chondrocytes were isolated, cultured, identified by toluidine blue staining and then transduced with lentivirus carrying the AR gene. The cell viability was determined using Cell Counting Kit-8, and cell apoptosis was assessed by flow cytometry analysis. The effects of AR overexpression on the expression of cartilage-specific proteins and some signalling molecules were evaluated by real-time PCR and Western blotting. Using 24 New Zealand rabbits, the regeneration of rabbit articular cartilage defects was further investigated in vivo and evaluated histologically. RESULTS: The overexpression of AR significantly reduced the apoptosis rate of chondrocytes but did not affect their proliferation. The overexpression of AR also promoted the expression of Sry-related HMG box 9, collagen II and aggrecan, decreased the expression of matrix metalloproteinase-13, and downregulated p-S6 and RICTOR. The experimental group with AR-overexpressing chondrocytes exhibited superior regeneration of cartilage defects. CONCLUSION AR overexpression can maintain the phenotype of chondrocytes and promote chondrogenesis in vitro and in vivo. mTOR-related signalling was inhibited.

BACKGROUND: The role of sex hormones and their receptors has drawn much attention in the process of cartilage regeneration. This study aimed to investigate the effect of androgen receptor (AR) on the chondrogenic ability of articular chondrocytes and the related mechanism. METHODS: Articular chondrocytes were isolated, cultured, identified by toluidine blue staining and then transduced with lentivirus carrying the AR gene. The cell viability was determined using Cell Counting Kit-8, and cell apoptosis was assessed by flow cytometry analysis. The effects of AR overexpression on the expression of cartilage-specific proteins and some signalling molecules were evaluated by real-time PCR and Western blotting. Using 24 New Zealand rabbits, the regeneration of rabbit articular cartilage defects was further investigated in vivo and evaluated histologically. RESULTS: The overexpression of AR significantly reduced the apoptosis rate of chondrocytes but did not affect their proliferation. The overexpression of AR also promoted the expression of Sry-related HMG box 9, collagen II and aggrecan, decreased the expression of matrix metalloproteinase-13, and downregulated p-S6 and RICTOR. The experimental group with AR-overexpressing chondrocytes exhibited superior regeneration of cartilage defects. CONCLUSION AR overexpression can maintain the phenotype of chondrocytes and promote chondrogenesis in vitro and in vivo. mTOR-related signalling was inhibited.

Objective:To establish a colon cancer cell line which overexpressing LINC01018 stably and study its biological characteristics.Methods:The expression of LINC01018 in HCoEpiC and HT-29 cells were detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR). HT-29 cells were infected with LINC01018 overexpression lentivirus to screen and establish HT-29 cell lines which overexpressing LINC01018 stably. The effect of LINC01018 on the proliferation, invasion and migration of HT-29 cells were detected by cell counting kit-8 (CCK-8) assay and Transwell assay separately. The expression of CDK6 and matrix metalloproteinase-2 (MMP-2) in HT-29 cells was detected by Western blot.Results:The expression of LINC01018 in HT-29 cells was significantly lower than that in the human colonic epithelial cells (HCoEpiC). HT-29-L18 cell lines which overexpressing LINC01018 stably was screened successfully. Overexpression of LINC01018 significantly inhibited the cell proliferation, invasion and migration, and reduced the protein expression of CDK6 and MMP-2 in HT-29 cells.Conclusions:The expression of LINC01018 was decreased abnormally in colon cancer cells. Up-regulation of LINC01018 expression can inhibit the proliferation, invasion and migration of colon cancer cells, which may be related to CDK6 and MMP-2.

Objective:To study the specific mechanism of LINC01018 involved in the pathogenesis of colon cancer.Methods:The expression of LINC01018 in colon cancer tissues and cells and normal colon tissues and cells were detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR). HT-29 cell line which overexpresses LINC01018 stably was established. RNA binding protein immunoprecipitation (RIP) assay was used to detect the interaction between LINC01018 and E2F1 protein. Dual luciferase assay was used to detect the regulatory effect of E2F1 on CDK6 promoter. The expression of E2F1 or CDK6 was up-regulated in HT-29 cell line which overexpresses LINC01018, then the proliferation, invasion and migration of HT-29 cells and the expression of CDK6 and matrix metalloproteinase-2 (MMP-2) in HT-29 cells were detected by cell counting method (CCK-8) assay, Transwell assay and Western blot.Results:The expression of LINC01018 was abnormally low in colon cancer tissues and cells. The result of RIP assay showed that LINC01018 interacted with E2F1 protein. The result of dual luciferase assay showed that E2F1 protein could enhance the efficiency of CDK6 promoter, and E2F1 had a positive regulatory effect on CDK6. Overexpression of LINC01018 could attenuate the positive regulatory effect of E2F1 on CDK6. Up-regulation of E2F1 or CDK6 expression could attenuate the effects of LINC01018 overexpression on the proliferation, invasion, migration and expression of CDK6 and MMP-2 in HT-29 cells.Conclusions:The expression of LINC01018 was abnormally low in colon cancer tissues and cells. LINC01018 may regulate the proliferation, invasion and migration of HT-29 cells through E2F1/CDK6/MMP-2 axis, and participate in the pathogenesis of colon cancer.