PI3K/AKT/mTOR pathway-related long non-coding RNAs: roles and mechanisms in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide with high prevalence and lethality. The oncogenic phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is a classic dysregulated pathway involved in the pathogenesis of HCC. However, the underlying mechanism for how PI3K/AKT/mTOR pathway aberrantly activates HCC has not been entirely elucidated. The recognition of the functional roles of long non-coding RNAs (lncRNAs) in PI3K/AKT/mTOR signaling axis sheds light on a new dimension to our understanding of hepatocarcinogenesis. In this review, we comprehensively summarize 67 dysregulated PI3K/AKT/mTOR pathway-related lncRNAs in HCC. Many studies have indicated that the 67 dysregulated lncRNAs show oncogenic or anti-oncogenic effects in HCC by regulation on epigenetic, transcriptional and post-transcriptional levels and they play pivotal roles in the initiation of HCC in diverse biological processes like proliferation, metastasis, drug resistance, radio-resistance, energy metabolism, autophagy and so on. Besides, many of these lncRNAs are associated with clinicopathological features and clinical prognosis in HCC, which may provide a potential future application in the diagnosis and therapy of HCC.

Keywords: 5-fluorouracil (PubChem CID3385); Capecitabine (PubChem CID60953); Doxorubicin (PubChem CID31703); Drug resistance; Gemcitabine (PubChem CID60750); Lenvatinib (PubChem CID9823820); Metastasis; Oncogenic; Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway; Post-transcriptional regulation; Prognosis; Retinoic acid (PubChem CID444795); Sorafenib (PubChem CID216239); Sunitinib (PubChem CID5329102); Trichostatin (PubChem CID444732).