The metastasis suppressor gene KISS-1 regulates osteosarcoma apoptosis and autophagy processes

Abstract

The expression of the metastasis suppressor gene KISS-1 in osteosarcoma cells during apoptosis and autophagy was evaluated. MG-63 osteosarcoma cells were transfected with either KISS-1 overexpression or KISS-1 knockdown expression vector in vitro, and compared with cell lines transfected with empty vector. After 12, 24, 48 and 72 h of cell culture, the cell proliferation was examined. The MTT method was used to detect apoptosis by flow cytometry, and the mRNA levels of apoptosis and autophagy markers caspase-3, Bcl-2, Bax, LC3 and Beclin1 were assessed by RT-PCR. Our results showed that cells in the control and low expression group kept proliferating during the cell culture period of 72 h, while the cells in the overexpression group progressively decreased in number. Also, the proliferation rate of the low expression group was significantly higher than that of the control group. The relative mRNA expression levels of caspase-3 and Bax mRNA in the control and low expression group showed no change (the expression was lowest in the low expression group). Moreover, the mRNA level of Bcl-2 increased in both cell groups. The mRNA expression levels of caspase-3 and Bax in the overexpression group were increased, and the level of Bcl-2 was reduced significantly. At the same time, the relative expression level of LC3 and Beclin1 mRNA in the control and low expression groups remained the same, and that of the overexpression group increased. The mRNA levels of LC3 and Beclin1 in the overexpression group were the highest, and that of the low expression group the lowest. The differences were statistically significant (P<0.05). Based on these results, we showed that KISS-1 inhibited the proliferation of osteosarcoma in vitro, probably by accelerating the processes of apoptosis and autophagy in the cells.

Comprehensive Analysis of Aerobic Exercise-Related Genes Identifies CDCA4 That Promotes the Progression of Osteosarcoma

“…Meanwhile, it is significantly related to the time of lung metastasis-free survival (MFS) ( Chen et al, 2019 ). Yin et al (2017) showed that the metastasis inhibitor gene KISS-1 modulated apoptosis and autophagy processes of osteosarcoma. However, the molecular mechanism of CDCA4 in osteosarcoma has not been clarified.…”

KISS1 protein expression is associated with worse prognosis in osteosarcoma patients: a long-term follow-up study

“…By down-regulating Gαq-p63RhoGEF-RhoA signaling pathways, Cho et al (16) found that the KISS1 receptor GPR54 gene could delay the development of breast cancer. Recently, Yin et al (17) reported that KISS1 inhibited the proliferation of OS in vitro by accelerating the processes of apoptosis and autophagy in the cells. Conversely, the high expression of KISS1/GPR54 showed poor prognosis in several other kinds of malignant tumors.…”

Controversial Role of Kisspeptins/KiSS-1R Signaling System in Tumor Development

“…Finally, KiSS-1 overexpression has been documented to regulate apoptosis by increasing caspase 3 and Bax and decreasing Bcl-2 and Bax mRNA levels in human osteosarcoma MG-62 and U2OS cells. In these cell lines, KiSS-1 overexpression reduces the extent of both cell proliferation and invasiveness ( 45 ).…”