Zhang Feifei, Chen Qian, Chen Peng, Liu Chaoqun, Wang Hui, Zhao Liang
Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Department of Pathology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, China.
J Cancer. 2022 Aug 8;13(10):3061-3072. doi: 10.7150/jca.65871. eCollection 2022.
Chemotherapy is an important treatment for gastric cancer (GC), but the primary and secondary drug resistance of tumours to chemotherapy seriously affects its curative effect. In recent years, the relationship between long noncoding RNAs (lncRNAs) and malignant tumours has received increasing attention. Based on accumulating evidence, lncRNAs are involved in the chemoresistance of GC, but the underlying mechanisms remain unclear. In this study, we identified the lncRNA colorectal neoplasia differentially expressed (CRNDE) as an important regulator of autophagy-associated chemoresistance in GC. Mechanistically, overexpression of CRNDE inhibits autophagy and induces apoptosis, thereby sensitizing GC cells to chemotherapy drugs. Moreover, E2F6, a classical transcriptional inhibitor, is confirmed to be upregulated in GC and represses the expression of CRNDE. The E2F6-CRNDE axis is clinically related to chemoresistant GC and poor outcomes in patients with advanced GC. Our findings suggest that the E2F6-CRNDE axis is a viable therapeutic target to protect against chemoresistance in GC.
化疗是胃癌（GC）的重要治疗方法，但肿瘤对化疗的原发性和继发性耐药严重影响其疗效。近年来，长链非编码RNA（lncRNAs）与恶性肿瘤之间的关系受到越来越多的关注。基于越来越多的证据，lncRNAs参与了GC的化疗耐药，但潜在机制仍不清楚。在本研究中，我们鉴定出长链非编码RNA结直肠肿瘤差异表达（CRNDE）是GC中自噬相关化疗耐药的重要调节因子。从机制上讲，CRNDE的过表达抑制自噬并诱导凋亡，从而使GC细胞对化疗药物敏感。此外，经典转录抑制剂E2F6在GC中被证实上调并抑制CRNDE的表达。E2F6-CRNDE轴在临床上与化疗耐药的GC以及晚期GC患者的不良预后相关。我们的研究结果表明，E2F6-CRNDE轴是预防GC化疗耐药的一个可行治疗靶点。
