Lung cancer is one of the most common cancers and has been the most common cause of cancer deaths for several decades. Recently, lung cancer-associated lncRNA 1 (LCAL1) has been identified to be overexpressed in lung cancer tissues, while inhibiting LCAL1 expression has shown potential to inhibiting lung cancer growth. However, the molecular mechanism between LCAL1 and lung cancer cell survival remains poorly understood. In the present study, we provided the first evidence that LCAL1 may support lung cancer survival via inhibiting the activity of AMP-activated protein kinase (AMPK). According to our results, LCAL1 may physically interact with the catalytic subunit of tumor suppressor AMPK, prevent AMPK activation by upstream kinase (liver kinase B1), and thus inhibit the downstream AMPK signaling network. Our study revealed that overexpressed LCAL1 may induce aerobic glycolysis in lung cancer cells through AMPK/HIF1α axis, enhance protein synthesis through AMPK/mTOR/S6K axis, and suppress autophagic cell death through AMPK/ULK1 pathway. All these alterations supported rapid proliferation of lung cancer cells, while knockdown of LCAL1 expression demonstrated the potential of inhibiting lung cancer growth by reversing the tumorigenic phenotypes triggered by the loss of AMPK activity, and could become a promising therapeutic strategy for lung cancer treatment.
Keywords: AMPK; LCAL1; LncRNA; Lung cancer.