Downregulation of lncRNA H19 Enhances Radiosensitivity in Colorectal Cancer by Inactivation of the ATR/CHK1 Signaling

Abstract

Radiotherapy (RT) is commonly used in the treatment of colorectal cancer (CRC), but the resistance of cancer cells to radiation remains a significant challenge in clinical practice. This study aimed to investigate whether long non-coding RNA (lncRNA) H19 could affect the sensitivity of CRC cells to radiation. The levels of H19 in CRC tissues and adjacent normal tissues, as well as in radioresistant and radiosensitive CRC tissues, were evaluated using RT-qPCR. The levels of H19 were found to be higher in CRC tissues compared to adjacent normal tissues, as well as in radioresistant CRC tissues compared to radiosensitive tissues. Depletion of H19 intensified the anti-tumor effects of radiation in CRC cells in vivo through further decreasing proliferation and enhancing apoptosis. In an HCT116 subcutaneous xenograft model, downregulation of H19 enhanced the anti-tumor effect of radiation in CRC in vivo. Mechanistically, H19 was observed to interact with ATR. Meanwhile, H19 deficiency resulted in the suppression of ATR and CHK1 phosphorylation in CRC cells, suggesting that H19 knockdown could potentially impair DNA damage repair through ATR/CHK1 signaling. Collectively, downregulation of H19 could enhance the sensitivity of CRC cells to RT by impeding DNA damage repair through the inactivation of the ATR/CHK1 signaling pathway.