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. 2020 Jun 15:12:4531-4540.
doi: 10.2147/CMAR.S248964. eCollection 2020.

LncRNA TDRG1 Promotes Proliferation, Invasion and Epithelial-Mesenchymal Transformation of Osteosarcoma Through PI3K/AKT Signal Pathway

Yan Huang  1 , Yong-Qiang Xu  2 , Si-Yin Feng  2 , Xiang Zhang  2 , Jiang-Dong Ni  1
Affiliations

LncRNA TDRG1 Promotes Proliferation, Invasion and Epithelial-Mesenchymal Transformation of Osteosarcoma Through PI3K/AKT Signal Pathway

Yan Huang et al. Cancer Manag Res. .

Abstract

Objective: This study aimed to investigate the effect of long non-coding TDRG1 on proliferation and migration of osteosarcoma cells through PI3K/AKT signaling pathway.

Materials and methods: Altogether 87 cases of osteosarcoma tissues and adjacent tissues were collected, and osteosarcoma cells and osteoblasts were purchased. The expression of LncRNA TDRG1 in tissues and cells was detected by RT-PCR. Si-NC, si-TDRG1, and Sh-TDRG1 were transfected into osteosarcoma cells. L740Y-P (activator of PI3K/AKT pathway) and LY294002 (inhibitor of PI3k/AKT pathway) were used to interfere with PI3k/Akt signaling pathway in osteosarcoma cells. qRT-PCR was used to detect the expression of TDRG1 in osteosarcoma tissues and cells. WB was used to detect the expression of p-PI3K, p-AKT, N-cadherin, E-Cadherin, vimentin, Bax, Caspase-3, and Bcl-2 in cells. CCK-8, Transwell and cell scratch tests were used to detect cell proliferation, invasion and migration, and flow cytometry was used to detect cell apoptosis.

Results: TDRG1 was highly expressed in osteosarcoma, and the levels of p-PI3K and p-AKT were also up-regulated. Cell experiments showed that inhibiting the expression of TDRG1 could inhibit the proliferation, invasion, migration and EMT of osteosarcoma cells, promote the apoptosis of cells, and up-regulating the expression of TDRG1 could promote the proliferation, invasion, migration and EMT of osteosarcoma cells and inhibit the apoptosis of cells. The 740Y-P intervention could reverse the inhibition of Si-TDRG1 on osteosarcoma cell proliferation, invasion, migration and EMT and the promotion of cell apoptosis. LY294002 intervention could reverse the promotion of Sh-TDRG1 on osteosarcoma cell proliferation, invasion, migration and EMT and the inhibition of cell apoptosis.

Conclusion: TDRG1 is highly expressed in osteosarcoma tissue. Silencing the expression of osteosarcoma can inhibit the proliferation, invasion, migration and EMT of osteosarcoma cells by inhibiting PI3K/AKT signaling pathway, which may be a new target for diagnosis and treatment of osteosarcoma.

Keywords: LncRNA TDRG1; PI3K/AKT; migration; osteosarcoma cells; proliferation.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Expression and significance of TDRG1 in osteosarcoma. (A) Expression of TDRG1 in osteosarcoma tissue; (B) Expression of TDRG1 in osteosarcoma cells; (C) ROC curve of TDRG1 in the diagnosis of osteosarcoma; (D) Influence of TDRG1 on the prognosis of osteosarcoma patients. *Indicates that P<0.05.
Figure 2
Figure 2
Effect of TDRG1 on proliferation and apoptosis of osteosarcoma cells. (A) Expression of TDRG1 in transfected osteosarcoma cells; (B) Effect of TDRG1 on the proliferation of osteosarcoma cells; (C) Effect of TDRG1 on apoptosis rate of osteosarcoma cells; (D) Effect of TDRG1 on apoptosis-related proteins in osteosarcoma cells. *Indicates that P<0.05.
Figure 3
Figure 3
Effect of TDRG1 on migration, invasion and EMT of osteosarcoma cells. (A) Influence of TDRG1 on the invasion of osteosarcoma cells; (B) Effect of TDRG1 on migration ability of osteosarcoma cells; (C) Effect of TDRG1 on EMT-related proteins in osteosarcoma cells. *Indicates that P<0.05.
Figure 4
Figure 4
Effect of TDRG1 on PI3K/AKT signaling pathway in osteosarcoma. (A) Influence of TDRG1 on PI3K/AKT signal pathway in MG-63; (B) Influence of TDRG1 on PI3K/AKT signal pathway in OS-732. *Indicates that P<0.05.
Figure 5
Figure 5
Effect of stimulation or inhibition of PI3K/AKT signaling pathway on osteosarcoma. (A) Expression of PI3K/AKT signaling pathway-related proteins after stimulation or inhibition of PI3K/AKT signaling pathway; (B) Effect of stimulation or inhibition of PI3K/AKT signaling pathway on proliferation ability of osteosarcoma cells; *Indicates P<0.05. (C) Effect of stimulation or inhibition of PI3K/AKT signaling pathway on the invasive ability of osteosarcoma cells; (D) Effect of stimulation or inhibition of PI3K/AKT signaling pathway on migration ability of osteosarcoma cells; (E) Effect of stimulation or inhibition of PI3K/AKT signaling pathway on apoptosis rate of osteosarcoma cells; (F) Effect of stimulation or inhibition of PI3K/AKT signaling pathway on apoptosis-related proteins in osteosarcoma cells; (G) Effect of stimulation or inhibition of PI3K/AKT signaling pathway on EMT-related proteins in osteosarcoma cells. *, #Indicates compared with Si-TDRG1+740Y-P, Sh-TDRG1+LY294002 and Si-NC groups, P< 0.05; *,#Indicates comparison P<0.05.
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