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Table 2 ncRNAs and HCC

From: Epigenetics of hepatocellular carcinoma

ncRNA Dysregulation in HCC Role(s) in HCC References
miRNAs
 miR-21 Upregulated expression Directly targets and represses MAP2K3 expression
Inhibition of miR-21 increased PTEN levels, affecting tumor cell proliferation and migration
[26, 27]
 miR-221/222 Upregulated expression Increased levels are associated with PTEN and TIMP3 downregulation
Targets p27 and induces tumor proliferation
[28,29,30]
 miR-224 Upregulated expression Promotes tumor cell proliferation, migration, invasion; inhibits apoptosis
Early HCC patients showed increased levels of serum miR-224; potential serum biomarker for early HCC detection
[31,32,33,34]
 miR-26 Downregulated expression Represses CDK6 and cyclin E1 expression, inhibiting G1/S transition
Inhibits expression of VEGFA, suppressing angiogenic and proliferative ability of the tumor
[35,36,37]
 miR-122 Downregulated expression Marker for hepatocyte-specific differentiation
Inhibits tumorigenic abilities of HCC cells
Loss of miR-122 enhances tumor cell migration and invasion
[38,39,40,41,42,43,44]
 miR-199 Downregulated expression Low levels correlate with poorer survival
Targets tumor-promoting PAK4, repressing the PAK4/Raf/MEK/ERK pathway
[45,46,47]
 miR-200a Downregulated expression Inhibits cell growth, migration, invasion and EMT by targeting Foxa2 and ZEB2 [48, 49]
lncRNAs
 HULC Upregulated expression Associated with tumor proliferation, angiogenesis and metastasis
Downregulates p18 tumor suppressor
Acts as miRNA sponge to sequester tumor-suppressive miRNAs, which could lead to activation of EMT and tumor angiogenesis
[50,51,52,53,54]
 HOTAIR Upregulated expression Recruits PRC2 and LSD1 complexes to mediate specific gene silencing
Involved in maintaining HCC tumor microenvironment via CCL2 expression
Inhibiting HOTAIR can suppress HCC proliferation and sensitise tumor cells to chemotherapy
[55,56,57,58,59]