Table 4.
miRNAs regulated by methylation in HCC.
| miRNA | Function/target | Impact of methylation | Status | Expression upon methylation |
|---|---|---|---|---|
| miR-148a | Acts as a tumor suppressor (Pan et al., 2014) | Enhanced tumorigenesis and HCC progression | Hypermethylation (He et al., 2015) | Downregulation |
| miR-375 | Acts as a tumor suppressor by inhibiting metastasis (Xie D. et al., 2017) 34 | Increased metastasis and HCC progression | Hypermethylation (He et al., 2015) | Downregulation |
| miR-195 | It acts as a tumor suppressor through metastasis inhibition (Wang M. et al., 2015) | Enhanced tumorigenesis and HCC progression | Hypermethylation (He et al., 2015) | Downregulation |
| miR-497 | It acts as a tumor suppressor by inhibiting metastasis angiogenesis (Yan et al., 2015) | Enhanced angiogenesis and metastasis | Hypermethylation (He et al., 2015) | Downregulation |
| miR-378 | Acts as a tumor suppressor (Li et al., 2013) | Enhanced proliferation | Hypermethylation (He et al., 2015) | Downregulation |
| miR-106b | Targets DAB2 (Sun et al., 2018) | Proliferation and migration | Hypomethylation (He et al., 2015) | Upregulation |
| miR-25 | Inhibits RhoGDI1 (Wang C. et al., 2015) | Promotion of both migration and invasion | Hypomethylation (He et al., 2015) | Upregulation |
| miR-93 | Targets PDCD4 (Ji et al., 2017) | Enhanced metastasis and invasion | Hypomethylation (He et al., 2015) | Upregulation |
| miR-23a | Acts as an oncomiR (Bao et al., 2014) | Onset of HCC | Hypomethylation (He et al., 2015) | Upregulation |
| miR-27a | Targets the peroxisome proliferator-activated receptor γ gene (Li S. et al., 2015) | Increased proliferation capacity | Hypomethylation (He et al., 2015) | Upregulation |
| miR-10a | Is reported to have several functions. It can promote migration and invasion, while inhibiting angiogenesis capacity in HCC and reduce metastasis capability by targeting Â1-integrin and MMP-2 (Tang, 2013) | After hypermethylation, metastasis and angiogenesis are expected to be reduced. On the other hand, invasion, and migration capabilities would be reduced | Hypermethylation (Shen et al., 2012) | Downregulation |
| miR-10b | Acts by targeting CSMD1, RhoC, uPAR, and MMPs (Liao et al., 2014; Zhu et al., 2016) | Hypermethylation of this miRNA is expected to reduce levels of migration, proliferation, and invasion potential | Hypermethylation (Shen et al., 2012) | Downregulation |
| miR-196b | Targets FOXP2 (Yu et al., 2018) | Decreased metastasis, proliferation, and migration potential | Hypermethylation (Shen et al., 2012) | Downregulation |
| miR-1 | It acts as an oncomiR (Hu et al., 2015) | Decreased proliferation and migration potential | Hypermethylation (Datta et al., 2008) | Silenced |
| miR-124 | Acts as a tumor suppressor by targeting Baculoviral IAP repeat containing 3 (BIRC3) gene (Cao et al., 2018) | Promotion of proliferation and migration potential | Hypermethylation (Furuta et al., 2010) | Silenced |
| miR-125b | Acts as a tumor suppressor by targeting (TAZ) transcriptional co-activator (Li J. et al., 2015) | Increased migration and invasion | Hypermethylation (Alpini et al., 2011) | Silenced |
| miR-203 | Acts as a tumor suppressor by targeting survivin (Wei W. et al., 2013) | Increased proliferation potential | Hypermethylation (Furuta et al., 2010) | Silenced |
| miR-1247 | Acts as a tumor suppressor with Wnt3 being its target (Chu et al., 2017) | Increased proliferation and invasion potential | Hypermethylation (Anwar et al., 2013) | Downregulation |
| miR-132 | Acts as a tumor suppressor by targeting PIK3R3 (Hu et al., 2015) | Increased proliferation, invasion, and migration potential | Hypermethylation (Wei X. et al., 2013) | Downregulation |
| miR-320 | Acts as a tumor suppressor where c-Myc is its target (Xie F. et al., 2017) | Increased proliferation and invasion | Hypermethylation (Shen et al., 2012) | Downregulation |
| miR-596 | No data available | No data available | Hypermethylation (Anwar et al., 2013) | Downregulation |
| miR-663 | Inhibits proliferation by targeting the HMGA2 gene (Huang et al., 2016) | Increased proliferation and invasion | Hypermethylation (Potapova et al., 2011) | Downregulation |
| miR-9 | Different data are reported: It may act as a tumor suppressor role by targeting TAZ (WWTR1) (Higashi et al., 2015). Moreover, it targets KLF17 and increases the migration and invasion properties (Sun et al., 2013) | Data reported that hypermethylation could lead to HCC progression (Higashi et al., 2015), while other reports suggested that hypermethylation can lead to reduced migration and invasion properties (Sun et al., 2013) | Hypermethylation (Anwar et al., 2013) | Downregulation |