Role of the long non-coding RNAs in regulation of Gemcitabine response in tumor cells

Chemotherapy is widely used as one of the first line therapeutic methods in cancer patients. However, chemotherapeutic resistance is one of the most common problems in cancer patients, which leads to the therapeutic failure and tumor relapse. Considering the side effects of chemotherapy drugs in normal tissues, it is required to investigate the molecular mechanisms involved in drug resistance to improve the therapeutic strategies in cancer patients. Long non-coding RNAs (lncRNAs) have pivotal roles in regulation of cellular processes associated with drug resistance. LncRNAs deregulations have been frequently reported in a wide range of chemo-resistant tumors. Gemcitabine (GEM) as a nucleoside analog has a wide therapeutic application in different cancers. However, GEM resistance is considered as a therapeutic challenge. Considering the role of lncRNAs in the occurrence of GEM resistance, in the present review we discussed the molecular mechanisms of lncRNAs in regulation of GEM response among cancer patients. It has been reported that lncRNAs have mainly an oncogenic role as the inducers of GEM resistance through direct or indirect regulation of transcription factors, autophagy, polycomb complex, and signaling pathways such as PI3K/AKT, MAPK, WNT, JAK/STAT, and TGF-β. This review paves the way to present the lncRNAs as non-invasive markers to predict GEM response in cancer patients. Therefore, lncRNAs can be introduced as the efficient markers to reduce the possible chemotherapeutic side effects in GEM resistant cancer patients and define a suitable therapeutic strategy among these patients.