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. 2020 Jun;19(6):4189-4194.
doi: 10.3892/ol.2020.11487. Epub 2020 Mar 27.

LINC00460 accelerates progression of ovarian cancer by activating transcriptional factor ZNF703

Xin Wang  1 , Xinghua Gan  1 , Chengcheng Liu  2 , Wenfeng Zhang  1
Affiliations

LINC00460 accelerates progression of ovarian cancer by activating transcriptional factor ZNF703

Xin Wang et al. Oncol Lett. 2020 Jun.

Abstract

Potential function of LINC00460 in the progression of ovarian cancer (OC) and its underlying mechanism were studied. LINC00460 level in OC tissues and normal ovarian tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation between LINC00460 level with tumor stage, tumor size and pathological subtypes of OC was analyzed. Potential influence of LINC00460 on proliferative ability and cell cycle progression was evaluated. In vivo tumorigenesis model was conducted by administration of A2780 cells transfected with sh-NC or sh-LINC00460 in nude mice. Predicted through JASPAR database, ZNF703 was screened out as the transcriptional factor binding to LINC00460 promoter region. Chromatin immunoprecipitation (ChIP) assay was performed to verify the binding relationship between ZNF703 and LINC00460. The potential role of ZNF703 in LINC00460-mediated OC progression was examined. LINC00460 was upregulated in OC tissues and cell lines. Its level increased with the deterioration of tumor stage and enlargement of tumor size. LINC00460 was highly expressed in serous ovarian cancer relative to other subtypes of OC. Knockdown of LINC00460 attenuated proliferative ability and arrested cell cycle of A2780 and HO8910 cells. ZNF703 was upregulated in OC tissues. ChIP assay showed pronounced enrichment of LINC00460 in ZNF703. Rescue experiments revealed that ZNF703 overexpression reversed the regulatory effects of LINC00460 on cellular behavior of OC cells. LINC00460 is upregulated in OC tissues and cell lines, which is closely related to tumor progression. It accelerates proliferative ability and cell cycle progression of OC cells via interacting with ZNF703.

Keywords: LINC00460; ZNF703; ovarian cancer; progression; proliferation.

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Figures

Figure 1.
Figure 1.
Upregulation of LINC00460 in OC tissues and cell lines. (A) Relative level of LINC00460 in OC tissues and normal ovarian tissues. (B) Relative level of LINC00460 in OC with stage I–II and stage III–IV. (C) Relative level of LINC00460 in OC with ≤5 cm tumor size and >5 cm. (D) Relative level of LINC00460 in serous OC and other subtypes of OC. (E) Relative level of LINC00460 in epithelial ovarian cell line and OC cell lines. OC, ovarian cancer (*P<0.05).
Figure 2.
Figure 2.
Silence of LINC00460 suppresses proliferative ability and arrests cell cycle of OC cells. (A) Transfection efficacy of si-LINC00460 in A2780 and HO8910 cells. A2780 and HO8910 cells were transfected with si-NC or si-LINC00460. (B) CCK-8 assay showing the viability in A2780 cells at day 1, 2, 3 and 4. (C) CCK-8 assay showing the viability in HO8910 cells at day 1, 2, 3 and 4. (D) Colony formation assay showing relative colonies in A2780 cells. (E) Colony formation assay showing relative colonies in HO8910 cells. (F) Flow cytometry showed cell ratio in S, G0/G1 and G2/M phase in A2780 cells. (G) Flow cytometry cell ratio in S, G0/G1 and G2/M phase in HO8910 cells. CCK-8, cell counting kit-8; OC, ovarian cancer (*P<0.05).
Figure 3.
Figure 3.
Knockdown of LINC00460 alleviates in vivo growth of OC. A2780 cells transfected with sh-NC or sh-LINC00460 were administered into nude mice. (A) Tumor weight in nude mice. (B) Tumor size in nude mice. (C) Transfection efficacy of sh-LINC00460 in A2780 cells. OC, ovarian cancer (*P<0.05).
Figure 4.
Figure 4.
ZNF703 participates in LINC0046-mediated progression of OC. (A) Relative level of ZNF703 in OC tissues and normal ovarian tissues. (B) Transfection efficacy of pcDNA-ZNF703 in A2780 and HO8910 cells. (C) Relative level of LINC00460 in A2780 and HO8910 cells transfected with NC or pcDNA-ZNF703. (D) Enrichment of LINC00460 in IgG and ZNF703 of A2780 cells. (E) Enrichment of LINC00460 in IgG and ZNF703 of HO8910 cells. (F) CCK-8 assay showing the viability in A2780 cells transfected with NC, si-LINC00460 or si-LINC00460+pcDNA-ZNF703. (G) CCK-8 assay showing the viability in HO8910 cells transfected with NC, si-LINC00460 or si-LINC00460+pcDNA-ZNF703. OC, ovarian cancer; CCK-8, cell counting kit-8 (*P<0.05).
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