LINC01137 involvement in pancreatic cancer stemness via the miR-7155-5p/KLF12/AKT axis

Abstract Pancreatic cancer, which most commonly refers to pancreatic ductal adenocarcinoma (PDAC), is one of the most malignant tumors, with a 5-year survival rate of about 4%. Pancreatic cancer stem cells play pivotal roles in chemoresistance and recurrence. Long non-coding RNAs (lncRNAs) have been identified as key regulators of the biological progression of various cancers. Recently, lncRNAs were found to be associated with cancer stem cells, which are related to chemoresistance. LINC01137 has been reported as an oncogene in oral squamous cell carcinoma. However, its function and underlying mechanisms in pancreatic cancer remain unclear. Online datasets were used to screen for cancer stem cell-associated lncRNAs and to confirm the relationship between LINC01137 and stem genes. Quantitative real-time PCR was performed to detect RNA expression. In situ hybridization and nucleocytoplasmic separation were used to determine subcellular location. Direct binding of LINC01137 to miR-7155-5p was verified using a dual-luciferase reporter assay. LINC01137 was upregulated in pancreatic cancer tissues and cell lines. Its high expression correlated with advanced pathological stages and poor prognosis. Induction of LINC01137 expression boosted pancreatic cancer stemness, chemoresistance, and proliferation. Mechanistically, LINC01137 exerted its biological function by binding to miR-7155-5p to activate the KLF12/PI3K/AKT pathway. KLF12 also promoted LINC01137 expression. LINC01137 and KLF12 were involved in promoting PDAC tumorigenesis. Our results suggested that LINC01137 functions as an oncogene in pancreatic cancer and identified its post-transcriptional regulatory mechanisms, which may contribute to targeted therapy for pancreatic cancer.