Abstract
Chemotherapy resistance after curative surgery is a major contributor to the mortality of colorectal cancer (CRC). Detailed mechanism studies of specific molecular alterations are critical to improving the available therapies for long-term disease administration. We explored the functional role of LINC01347 in chemotherapy resistance of CRC. Elevated LINC01347 expression was correlated with CRC disease progression during chemotherapy treatment. However, the functional role of LINC01347 and mechanism remained undefined. In this study, we demonstrated that elevated LINC01347 expression was correlated with late clinical stage and poor prognosis in CRC tumor tissues with TCGA data. Exogenous LINC01347 expression promoted cell proliferation and 5-FU resistance of CRC cells, while LINC01347 knockdown attenuated cell growth and 5-FU resistance in vitro and in vivo. Molecular analysis indicated that LINC01347 participated in the transcriptional regulation of LOXL2 by sponging miR-328-5p. LOXL2 knockdown impaired the LINC01347 overexpression induced 5-FU resistance in CRC cells. The clinical analysis supported miR-328-5p/LOXL2 as a candidate biomarker for chemotherapy resistance of CRC patients. Our study provided a molecular basis for the development of 5-FU based chemotherapy resistance in CRC by LINC01347/miR-328/LOXL2 axis. We identified LINC01347 as a prognostic biomarker and potential therapeutic target against 5-FU based chemotherapy resistance of CRC.