Department of Laboratory Medicine, General Hospital of Southern Theatre Command of PLA, 510010 Guangzhou, Guangdong, China; Department of Laboratory Medicine, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Huiai Hospital, 510370 Guangzhou, Guangdong, China.
Department of Laboratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, 511518 Qingyuan, Guangdong, China.
Gene. 2023 Apr 15;860:147227. doi: 10.1016/j.gene.2023.147227. Epub 2023 Jan 26.
Circulating long noncoding RNAs (lncRNAs) have been reported to serve as biomarkers for cancer diagnosis. Here, we identified the clinical diagnostic value and biological function of lncRNA T376626 in triple-negative breast cancer (TNBC).
A genome-wide lncRNA microarray was used to screen promising serum-based lncRNA biomarkers. The expression of candidate serum lncRNAs was validated in 282 breast cancer (BC) patients and 78 healthy subjects. The diagnostic value of serum lncRNA T376626 was determined by receiver operating characteristic (ROC) curve. RNA fluorescent in situ hybridization (FISH) and RNAScope ISH assays were conducted to examine the expression and localization of lncRNA T376626 in TNBC cells and BC tissues. Kaplan-Meier analysis was conducted to evaluate the relationship between lncRNA T376626 and BC patients' overall survival (OS) rate. CCK-8, colony-forming, wound healing and Transwell assays were performed to investigate the biological function of lncRNA T376626 on cell proliferation, migration, and invasion in two TNBC cell lines. Cell apoptosis-, cell cycle- and epithelial-mesenchymal transition (EMT)-related biomarkers were quantified by western blots. The lncRNA T376626 binding proteins were screened and identified by RNA pulldown.
LncRNA T376626 level was significantly higher in TNBC serums and tissues. Higher levels of lncRNA T376626 were positively associated with a higher pathological differentiation stage, more aggressive molecular subtype, and poor prognosis in BC and TNBC patients. The area under the curve (AUC) of serum lncRNA T376626 was 0.842. Overexpression (Knockdown) of lncRNA T376626 significantly promoted (inhibited) TNBC cell proliferation, migration, and invasion, possibly by regulating several cell cycle, cell apoptosis and EMT biomarkers. LAMC2 were identified as lncRNA T376626-binding proteins. LAMC2 facilitated TNBC proliferation and metastasis through lncRNA T376626.
LncRNA T376626 may serve as a TNBC serum-based diagnostic and prognostic biomarker and play an oncogenic role in TNBC progression through binding to LAMC2.
循环长链非编码 RNA（lncRNA）已被报道可作为癌症诊断的生物标志物。在这里，我们鉴定了 lncRNA T376626 在三阴性乳腺癌（TNBC）中的临床诊断价值和生物学功能。
使用全基因组 lncRNA 微阵列筛选有前途的基于血清的 lncRNA 生物标志物。在 282 名乳腺癌（BC）患者和 78 名健康受试者中验证候选血清 lncRNA 的表达。通过接收者操作特征（ROC）曲线确定血清 lncRNA T376626 的诊断价值。通过 RNA 荧光原位杂交（FISH）和 RNAScope ISH 检测来检查 TNBC 细胞和 BC 组织中 lncRNA T376626 的表达和定位。Kaplan-Meier 分析用于评估 lncRNA T376626 与 BC 患者总生存率（OS）之间的关系。通过 CCK-8、集落形成、划痕愈合和 Transwell 测定来研究 lncRNA T376626 在两种 TNBC 细胞系中的细胞增殖、迁移和侵袭中的生物学功能。通过蛋白质印迹定量细胞凋亡、细胞周期和上皮-间充质转化（EMT）相关生物标志物。通过 RNA 下拉筛选和鉴定 lncRNA T376626 的结合蛋白。
lncRNA T376626 在 TNBC 血清和组织中的水平明显升高。lncRNA T376626 水平升高与 BC 和 TNBC 患者更高的病理分化阶段、更具侵袭性的分子亚型和不良预后呈正相关。血清 lncRNA T376626 的曲线下面积（AUC）为 0.842。lncRNA T376626 的过表达（敲低）显著促进（抑制）了 TNBC 细胞的增殖、迁移和侵袭，这可能是通过调节几个细胞周期、细胞凋亡和 EMT 生物标志物来实现的。LAMC2 被鉴定为 lncRNA T376626 的结合蛋白。LAMC2 通过 lncRNA T376626 促进 TNBC 的增殖和转移。
lncRNA T376626 可作为 TNBC 基于血清的诊断和预后生物标志物，并通过与 LAMC2 结合在 TNBC 进展中发挥致癌作用。
