Li Zhi-Hua, Yu Ni-Si, Deng Qing, Zhang Yulu, Hu Yang-Yang, Liu Gang, Huang Kedi
Department of Breast Surgery, Third Hospital of Nanchang, JiangXi Breast Specialist Hospital, Nanchang, China.
Key Laboratory of Breast Diseases in Jiangxi Province, Third Hospital of Nanchang, Nanchang, China.
Front Oncol. 2020 Nov 24;10:592757. doi: 10.3389/fonc.2020.592757. eCollection 2020.
Chemoresistance is considered to be a major cause of the recurrence and metastasis of breast cancer (BC). LncRNA SNHG7 has been reported to be upregulated in breast cancer and to promote tumor progression and metastasis. Nevertheless, the function and potential regulatory mechanism of SNHG7 in BC drug resistance are still largely unclear. This study indicated that SNHG7 was highly expressed in chemoresistant BC tissues and cells. Upregulated SNHG7 might predict a low pCR rate and poor clinical outcome in BC patients. Knockdown of SNHG7 enhanced drug sensitivity and drug-induced apoptosis in chemoresistant BC cells. In terms of the mechanism, miR-34a was found to be a target of SNHG7 and its expression in breast cancer tissues and chemoresistant cell lines was negatively correlated with SNHG7 expression. Importantly, sh-SNHG7 upregulated miR-34a expression, reduced the percentages of CD44/CD24cells, and inhibited sphere-formation and stem cell factor (Oct4, Nanog, SOX2) expression. Functional loss experiments showed that the repressive effect of SNHG7 knockdown on BC cell stemness was partially reversed by transfection with miR-34a inhibitors. In summary, this study indicated that SNHG7 contributed to the chemoresistance of BC and mediated chemoresistance and cancer stemness by sponging miR-34a.
化疗耐药被认为是乳腺癌(BC)复发和转移的主要原因。据报道,长链非编码RNA SNHG7在乳腺癌中上调,并促进肿瘤进展和转移。然而,SNHG7在BC耐药中的功能和潜在调控机制仍不清楚。本研究表明,SNHG7在化疗耐药的BC组织和细胞中高表达。SNHG7上调可能预示着BC患者的低pCR率和不良临床结局。敲低SNHG7可增强化疗耐药BC细胞的药物敏感性和药物诱导的凋亡。在机制方面,发现miR-34a是SNHG7的靶标,其在乳腺癌组织和化疗耐药细胞系中的表达与SNHG7表达呈负相关。重要的是,sh-SNHG7上调miR-34a表达,降低CD44/CD24细胞百分比,并抑制球体形成和干细胞因子(Oct4、Nanog、SOX2)表达。功能缺失实验表明,用miR-34a抑制剂转染可部分逆转SNHG7敲低对BC细胞干性的抑制作用。总之,本研究表明SNHG7促进了BC的化疗耐药,并通过海绵吸附miR-34a介导化疗耐药和癌症干性。