lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway

Abstract

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.

A Radioresponse-Related lncRNA Biomarker Signature for Risk Classification and Prognosis Prediction in Non-Small-Cell Lung Cancer

“…In the present study, our constructed risk signature consisted of four lncRNAs which were closely related to NSCLC prognosis. Among these five lncRNAs, CASC19 related AMPK-mTOR pathway [46]. In addition, CASC19 also has an oncogenic effect on NSCLC.…”

“…In pancreatic cancer (PC), CASC19 could facilitate malignant growth and metastasis of PC via miR-148b/E2F7 ceRNA axis with sponge activity [ 45 ]. As suggested by Liu et al, CASC19 was highly expressed in radioresistant nasopharyngeal carcinoma (NPC) cells and could confer radioresistance in NPC through autophagy-related AMPK-mTOR pathway [ 46 ]. In addition, CASC19 also has an oncogenic effect on NSCLC.…”

Identification of an Epithelial-Mesenchymal Transition-Related Long Non-coding RNA Prognostic Signature for Hepatocellular Carcinoma

“…The lncRNA CASC19 was widely reported and markedly upregulated in multiple tumor tissues and cells, higher CASC19 expression is associated with tumor progression and poorer prognoses, including colorectal cancer, advanced gastric cancer, non-small lung cancer cells, and pancreatic cancer [32][33][34][35]. Two other studies revealed that a high expression level of CASC19 was positively correlated with radio resistance in cervical cancer and nasopharyngeal carcinoma [36,37]. However, the other seven prognostic EMT-related lncRNAs (AC103760.…”

Emerging role of lncRNAs in drug resistance mechanisms in head and neck squamous cell carcinoma

“…In LSCC, GAS5 inhibited the viability of AMC-HN-8 cells and induced apoptosis, acting as a tumor suppressor by regulating the miR-26a-5o/ULK2 axis ( 130 ). Conversely, CASC19 suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway, contributing to the radioresistance of NPC by regulating autophagy ( 114 ).…”