J Cancer 2022; 13(10):3061-3072. doi:10.7150/jca.65871 This issue

Research Paper

The lncRNA CRNDE is regulated by E2F6 and sensitizes gastric cancer cells to chemotherapy by inhibiting autophagy

Feifei Zhang1*, Qian Chen2,3*, Peng Chen1*, Chaoqun Liu3, Hui Wang4, Liang Zhao2,3✉

1. Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
2. Department of Pathology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, China.
3. Department of Pathology & Guangdong Province Key Laboratory of Molecular Tumor Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
4. Department of Medical Oncology, Affiliated Tumour Hospital of Guangzhou Medical University, Guangzhou, China.
*These authors are contributed equally to this work.

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Zhang F, Chen Q, Chen P, Liu C, Wang H, Zhao L. The lncRNA CRNDE is regulated by E2F6 and sensitizes gastric cancer cells to chemotherapy by inhibiting autophagy. J Cancer 2022; 13(10):3061-3072. doi:10.7150/jca.65871. Available from https://www.jcancer.org/v13p3061.htm

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Graphic abstract

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.

Keywords: LncRNA, CRNDE, Gastric cancer, Autophagy, Chemoresistance