Prognostic Value of LINC01140 in Colorectal Cancer and Its Regulatory Effect on Chemotherapy Resistance via miR‐942‐5p/NRXN1

ABSTRACT

Long non‐coding RNAs play a wide role in colorectal cancer (CRC). But the function of LINC01140 in CRC has not yet been revealed. This study aims to explore the functional mechanism of LINC01140 in CRC, with the expectation of providing new therapeutic targets for CRC. The histological expression of LINC01140 was examined to evaluate its clinical predictive value in CRC prognosis. The potential downstream (miR‐942‐5p/NRXN1) of LINC01140 were predicted using bioinformatics methods, and their targeted relationship was verified through RNA pull‐down and dual luciferase reporter assays. The effects of this regulatory axis on the functions of CRC cells and cancer‐associated fibroblasts (CAFs) were evaluated through CCK‐8 or Transwell experiments. Cisplatin‐ and oxaliplatin‐ tolerant CRC cell lines were established for chemotherapy resistance studies. LINC01140 exhibited significant downregulation in CRC tumor tissues and was associated with an unfavorable prognosis. The chi‐square test revealed the association between LINC01140 and TNM stage as well as lymphatic metastasis. Overexpression of LINC01140 suppressed the proliferation and migration/invasion capacities of CRC cells and alleviated their chemotherapy resistance, reducing the IC50 values of cisplatin and oxaliplatin for drug‐resistant cells. LINC01140 acted as a sponge for miR‐942‐5p and inhibited the functions of CRC cells and CAFs by upregulating NRXN1. Co‐culture with CAFs promoted the chemoresistance of CRC cells. Upregulation of LINC01140/NRXN1 or inhibition of miR‐942‐5p in CAFs attenuated this ability. LINC01140 may serve as a biomarker in CRC prognosis. It suppresses CRC cells and hinders CAF activation, alleviating chemotherapy resistance by regulating miR‐942‐5p/NRXN1.