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| Effect of LincRNA 00312 on the Malignant Biological Behavior of Ovarian Cancer Cells by Regulating SOSTDC1-Mediated BMP-Smads Axis |
| NIU Lina, CHEN Zhuojing, XU Wangxin, et al |
| Yuncheng Central Hospital Affiliated to Shanxi Medical University, Shanxi Yuncheng 044000, China |
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Abstract Objective: To investigate the effect of long noncoding RNA (LncRNA) 00312 on the malignant biological behavior of ovarian cancer (OC) cells by regulating target sclerostin domain containing protein 1 (SOSTDC1)-mediated bone morphogenetic protein (BMP)-smads axis. Methods: The cancer tissues and adjacent tissues of 15 patients undergoing ovarian cancer radical operation in Yuncheng Central Hospital from September 2021 to December 2022 were collected, and human normal ovarian epithelial cells (IOSE80) and EC cells (SKOV3 and OVCAR) were selected as target cells. The expression of LincRNA 00312 in OC cancer and adjacent tissues, SKOV3 and OVCAR was analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). SKOV3 cells were divided into si-NC group, si-LincRNA 00312 group, si-LincRNA 00312 + si-SOSTDC1 group, OE-NC group and OE-SOSTDC1 group. Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to analyze the possible downstream pathways of LincRNA 00312. Western blot was used to detect the expression of SOSTDC1 and BMP-smad pathway-related proteins in OC tissues and SKOV3 cells in each group. Colony formation assay, scratch assay and Transwell assay were used to detect the proliferation, migration and invasion of SKOV3 cells in each group, respectively. The targeting effects of LincRNA 00312 and SOSTDC1 were detected by bioinformatics prediction, dual luciferase reporter gene and RNA-protein pull-down assay. Results: The expression of LincRNA 00312 in OC cancer tissues was significantly higher than that in adjacent tissues (t=7.288, P<0.05), which in SKOV3 and OVCAR3 cells was significantly increased than that in IOSE80 cells (t=27.805, 8.860, all P<0.05). KEGG pathway analysis showed that LincRNA 00312 was mainly related to BMP-smad signaling pathway, transcription disorders in tumors and mitogen-activated protein kinases (MAPK) signaling pathway. Bioinformatics analysis showed that there was a possible binding site between LincRNA 00312 and SOSTDC1 mRNA sequence. Compared with the adjacent tissues, the mRNA-protein expression levels of SOSTDC1 in cancer tissues were significantly decreased (t=23.653, 27.498, all P<0.05), and the protein expression levels of bone morphogenetic protein-2 (BMP2), BMP4, BMP7, amad1 domain-containing protein 1 (amad1) / 5 / 9 and p-smad1 / 5 / 9 were significantly increased (t=5.952, 7.322, 8.024, 7.094 and 5.512, all P<0.05). Compared with the si-NC group, the si-LincRNA 00312 group had significantly decreased colony numbers, wound healing rate, number of invasive cells (t=6.914, 4.729, 11.321, all P<0.05). The dual luciferase reporter gene found that the luciferase activity of pGL3-SOSTDC1-WT in SKOV3 cells in OE-SOSTDC1 group was significantly lower than that in OE-NC group (t=19.744, P<0.05). RNA-protein pull-down assay showed that the enrichment multiple of SOSTDC1 in transfected Bio-LincRNA 00312-WT cells was significantly higher than that in transfected Bio-LincRNA 00312-MUT cells (t=36.374, P<0.05). Compared with the OE-NC group, the OE-SOSTDC1 group had significantly increased expression of SOSTDC1 protein in SKOV3 cells ( t=39.491, P<0.05 ), and decreased expression of BMP2, BMP4, BMP7, amad1 / 5 / 9 and p-SAMD1 / 5 / 9 proteins (t=19.696, 19.752, 14.203, 45.928 and 21.637, all P<0.05). Compared with the si-LincRNA 00312 group, the si-LincRNA 00312 + si-SOSTDC1 group presented significantly increased colony numbers, migration rate, number of invasive cells and the expression of BMP2, BMP4, BMP7, smad1 / 5 / 9 and p-smad1 / 5 / 9 proteins (t=8.911, 8.193, 8.873, 14.203, 12.222, 20.821, 19.365 and 31.225, all P<0.05). Conclusion: The upregulated LincRNA 00312 in OC tissues can promote cancer cell proliferation, migration and invasion by regulating the SOSTDC1-mediated BMP-smad signaling pathway.
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2024, Vol. 30 
