Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
J Cell Mol Med. 2021 May;25(9):4434-4443. doi: 10.1111/jcmm.16511. Epub 2021 Apr 8.
Our previous studies have shown that the Adipose-derived mesenchymal stem cells (ADSCs) can regulate metastasis and development of ovarian cancer. However, its specific mechanism has yet to be fully revealed. In this study, an RNA-seq approach was adopted to compare the differences in mRNA levels in ovarian cancer cells being given or not given ADSCs. The mRNA level of paired box 8 (PAX8) changed significantly and was confirmed as an important factor in tumour-inducing effect of ADSCs. In comparison with the ovarian cancer cells cultured in the common growth medium, those cultured in the medium supplemented with ADSCs showed a significant increase of the PAX8 level. Moreover, the cancer cell growth could be restricted, even in the ADSC-treated group (P < .05), by inhibiting PAX8. In addition, an overexpression of PAX8 could elevate the proliferation of ovarian cancer cells. Moreover, Co-IP assays in ovarian cancer cells revealed that an interaction existed between endogenous PAX8 and TAZ. And the PAX8 levels regulated the degradation of TAZ. The bioluminescence images captured in vivo manifested that the proliferation and the PAX8 expression level in ovarian cancers increased in the ADMSC-treated group, and the effect of ADSCs in promoting tumours was weakened through inhibiting PAX8. Our findings indicate that the PAX8 expression increment could contribute a role in promoting the ADSC-induced ovarian cancer cell proliferation through TAZ stability regulation.
我们之前的研究表明脂肪间充质干细胞(ADSCs)可以调节卵巢癌细胞的转移和发展。然而,其具体机制尚未完全揭示。在这项研究中,我们采用 RNA-seq 方法比较了给予或未给予 ADSCs 的卵巢癌细胞之间 mRNA 水平的差异。配对盒 8(PAX8)的 mRNA 水平变化显著,被确认为 ADSCs 诱导肿瘤效应的重要因素。与在普通生长培养基中培养的卵巢癌细胞相比,在补充 ADSCs 的培养基中培养的细胞中 PAX8 水平显著增加。此外,通过抑制 PAX8 可以限制癌细胞的生长,即使在 ADSC 处理组中也是如此(P<.05)。此外,PAX8 的过表达可以提高卵巢癌细胞的增殖能力。此外,在卵巢癌细胞中的 Co-IP 实验表明,内源性 PAX8 和 TAZ 之间存在相互作用。并且 PAX8 水平调节 TAZ 的降解。体内生物发光图像表明,在 ADMSC 处理组中,卵巢癌的增殖和 PAX8 表达水平增加,通过抑制 PAX8 减弱了 ADSCs 促进肿瘤的作用。我们的研究结果表明,PAX8 表达的增加可能通过 TAZ 稳定性调节促进 ADSC 诱导的卵巢癌细胞增殖。