长链非编码RNA ADAMTS9-AS2通过调控核糖体蛋白L22来调节三阴性乳腺癌进展并控制转化生长因子-β信号通路。
The lncRNA ADAMTS9-AS2 Regulates RPL22 to Modulate TNBC Progression Controlling the TGF-β Signaling Pathway.
作者信息
Ni Kan, Huang Zhiqi, Zhu Yichun, Xue Dandan, Jin Qin, Zhang Chunhui, Gu Changjiang
机构信息
Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, China.
Department of General Surgery, Nantong First people's hospital, The Second Affiliated Hospital of Nantong University, Nantong, China.
出版信息
Front Oncol. 2021 Jun 9;11:654472. doi: 10.3389/fonc.2021.654472. eCollection 2021.
BACKGROUND
Long non-coding RNAs (lncRNAs) are key regulators of triple-negative breast cancer (TNBC) progression, but further work is needed to fully understand the functional relevance of these non-coding RNAs in this cancer type. Herein, we explored the functional role of the lncRNA ADAMTS9-AS2 in TNBC.
METHODS
Next-generation sequencing was conducted to compare the expression of different lncRNAs in TNBC tumor and paracancerous tissues, after which ADAMTS9-AS2differential expression in these tumor tissues was evaluated qPCR. The functional role of this lncRNA was assessed by overexpressing it and FISH and PCR were used to assess the localization of ADAMTS9-AS2within cells. Downstream targets of ADAMTS9-AS2 signaling were identified RNA pulldown assays and transcriptomic sequencing.
RESULTS
The expression ofADAMTS9-AS2 was decreased in TNBC tumor samples (P < 0.05), with such downregulation being correlated with TNM stage, age, and tumor size. Overexpressing ADAMTS9-AS2 promoted the apoptotic death and cell cycle arrest of tumor cells and inhibited tumor growth From a mechanistic perspective, ADAMTS9-AS2 was found to control the expression of RPL22 and to thereby modulate TGF-β signaling to control TNBC progression.
CONCLUSION
ADAMTS9-AS2 controls the expression of RPL22 and thereby regulates TNBC malignancy the TGF-β signaling pathway.
背景
长链非编码RNA（lncRNAs）是三阴性乳腺癌（TNBC）进展的关键调节因子，但仍需进一步研究以全面了解这些非编码RNA在该癌症类型中的功能相关性。在此，我们探讨了lncRNA ADAMTS9-AS2在TNBC中的功能作用。
方法
进行下一代测序以比较TNBC肿瘤组织和癌旁组织中不同lncRNAs的表达，之后通过qPCR评估这些肿瘤组织中ADAMTS9-AS2的差异表达。通过过表达该lncRNA评估其功能作用，并使用FISH和PCR评估ADAMTS9-AS2在细胞内的定位。通过RNA下拉实验和转录组测序鉴定ADAMTS9-AS2信号的下游靶点。
结果
TNBC肿瘤样本中ADAMTS9-AS2的表达降低（P < 0.05），这种下调与TNM分期、年龄和肿瘤大小相关。过表达ADAMTS9-AS2可促进肿瘤细胞的凋亡死亡和细胞周期停滞，并抑制肿瘤生长。从机制角度来看，发现ADAMTS9-AS2可控制RPL22的表达，从而调节TGF-β信号以控制TNBC进展。
结论
ADAMTS9-AS2通过TGF-β信号通路控制RPL22的表达，从而调节TNBC的恶性程度。
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