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Abstract：
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with higher aggressiveness and poorer outcomes. Recently, long non-coding RNAs (lncRNAs) have become the crucial gene regulators in the progression of human cancers. However, the function and underlying mechanisms of lncRNAs in TNBC remains unclear.
Based on public databases and bioinformatics analyses, the low expression of lncRNA MIDEAS-AS1 in breast cancer tissues was detected and further validated in a cohort of TNBC tissues. The effects of MIDEAS-AS1 on proliferation, migration, invasion were determined by in vitro and in vivo experiments. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were carried out to reveal the interaction between MIDEAS-AS1 and MATR3. Luciferase reporter assay, Chromatin immunoprecipitation (ChIP) and qRT-PCR were used to evaluate the regulatory effect of MIDEAS-AS1/MATR3 complex on NCALD.
LncRNA MIDEAS-AS1 was significantly downregulated in TNBC, which was correlated with poor overall survival (OS) and progression-free survival (PFS) in TNBC patients. MIDEAS-AS1 overexpression remarkably inhibited tumor growth and metastasis in vitro and in vivo. Mechanistically, MIDEAS-AS1 mainly located in the nucleus and interacted with the nuclear protein MATR3. Meanwhile, NCALD was selected as the downstream target, which was transcriptionally regulated by MIDEAS-AS1/MATR3 complex and further inactivated NF-κB signaling pathway. Furthermore, rescue experiment showed that the suppression of cell malignant phenotype caused by MIDEAS-AS1 overexpression could be reversed by inhibition of NCALD.
Collectively, our results demonstrate that MIDEAS-AS1 serves as a tumor-suppressor in TNBC through modulating MATR3/NCALD axis, and MIDEAS-AS1 may function as a prognostic biomarker for TNBC.
Based on public databases and bioinformatics analyses, the low expression of lncRNA MIDEAS-AS1 in breast cancer tissues was detected and further validated in a cohort of TNBC tissues. The effects of MIDEAS-AS1 on proliferation, migration, invasion were determined by in vitro and in vivo experiments. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were carried out to reveal the interaction between MIDEAS-AS1 and MATR3. Luciferase reporter assay, Chromatin immunoprecipitation (ChIP) and qRT-PCR were used to evaluate the regulatory effect of MIDEAS-AS1/MATR3 complex on NCALD.
LncRNA MIDEAS-AS1 was significantly downregulated in TNBC, which was correlated with poor overall survival (OS) and progression-free survival (PFS) in TNBC patients. MIDEAS-AS1 overexpression remarkably inhibited tumor growth and metastasis in vitro and in vivo. Mechanistically, MIDEAS-AS1 mainly located in the nucleus and interacted with the nuclear protein MATR3. Meanwhile, NCALD was selected as the downstream target, which was transcriptionally regulated by MIDEAS-AS1/MATR3 complex and further inactivated NF-κB signaling pathway. Furthermore, rescue experiment showed that the suppression of cell malignant phenotype caused by MIDEAS-AS1 overexpression could be reversed by inhibition of NCALD.
Collectively, our results demonstrate that MIDEAS-AS1 serves as a tumor-suppressor in TNBC through modulating MATR3/NCALD axis, and MIDEAS-AS1 may function as a prognostic biomarker for TNBC.
摘要：
背景：三阴性乳腺癌（TNBC）是乳腺癌的一种亚型，具有较高的侵袭性和较差的预后。最近,长链非编码RNA（lncRNAs）已成为人类癌症进展的关键基因调节因子。然而,lncRNAs在TNBC中的功能和潜在机制尚不清楚.
方法：基于公共数据库和生物信息学分析，检测到lncRNAMIDEAS-AS1在乳腺癌组织中的低表达,并在TNBC组织队列中进一步验证.MIDEAS-AS1对增殖的影响，迁移,通过体外和体内实验确定侵袭。进行RNA下拉测定和RNA免疫沉淀(RIP)测定以揭示MIDEAS-AS1和MATR3之间的相互作用。荧光素酶报告基因测定，染色质免疫沉淀（ChIP）和qRT-PCR用于评估MIDEAS-AS1/MATR3复合物对NCALD的调节作用。
结果：LncRNAMIDEAS-AS1在TNBC中显著下调，这与TNBC患者的总生存期（OS）和无进展生存期（PFS）相关。MIDEAS-AS1过表达在体外和体内均显着抑制肿瘤的生长和转移。机械上,MIDEAS-AS1主要位于细胞核中，并与核蛋白MATR3相互作用。同时,NCALD被选为下游目标，受MIDEAS-AS1/MATR3复合物的转录调控，并进一步灭活NF-κB信号通路。此外，拯救实验表明，MIDEAS-AS1过表达引起的细胞恶性表型抑制可以通过抑制NCALD逆转。
结论：总的来说，我们的结果表明，MIDEAS-AS1通过调节MATR3/NCALD轴在TNBC中充当肿瘤抑制因子，和MIDEAS-AS1可能作为TNBC的预后生物标志物。
方法：基于公共数据库和生物信息学分析，检测到lncRNAMIDEAS-AS1在乳腺癌组织中的低表达,并在TNBC组织队列中进一步验证.MIDEAS-AS1对增殖的影响，迁移,通过体外和体内实验确定侵袭。进行RNA下拉测定和RNA免疫沉淀(RIP)测定以揭示MIDEAS-AS1和MATR3之间的相互作用。荧光素酶报告基因测定，染色质免疫沉淀（ChIP）和qRT-PCR用于评估MIDEAS-AS1/MATR3复合物对NCALD的调节作用。
结果：LncRNAMIDEAS-AS1在TNBC中显著下调，这与TNBC患者的总生存期（OS）和无进展生存期（PFS）相关。MIDEAS-AS1过表达在体外和体内均显着抑制肿瘤的生长和转移。机械上,MIDEAS-AS1主要位于细胞核中，并与核蛋白MATR3相互作用。同时,NCALD被选为下游目标，受MIDEAS-AS1/MATR3复合物的转录调控，并进一步灭活NF-κB信号通路。此外，拯救实验表明，MIDEAS-AS1过表达引起的细胞恶性表型抑制可以通过抑制NCALD逆转。
结论：总的来说，我们的结果表明，MIDEAS-AS1通过调节MATR3/NCALD轴在TNBC中充当肿瘤抑制因子，和MIDEAS-AS1可能作为TNBC的预后生物标志物。
