Copyright ©The Author(s) 2019.
World J Hepatol. Apr 27, 2019; 11(4): 344-358
Published online Apr 27, 2019. doi: 10.4254/wjh.v11.i4.344
Table 2 miRNAs and autophagy in hepatocellular carcinoma cell drug resistance
miRNAExpression Level in HCCEffect on autophagyInvolvement in drug resistanceRef.
miR26a/bDownregulated in tissues and cell lines (HepG2, Hep3B, MHCC97-H and SMCC-7721), also by chemotherapeutic drugs and autophagy inhibitorsInhibited autophagy, by targeting the expression of ULK1, the key initiator of autophagySensitized HepG2 cells and tumors to apoptosis induced by DOX through targeting autophagy[53,54]
miR199a-5pDownregulated in HepG2 and HuH-7 cells and tissues, also by chemotherapeutic drugsInhibited cisplatin-induced autophagy, by interacting with the 3’UTR region of ATG7 transcript (an autophagy related gene)Protected HepG2 and HuH-7 cells from cisplatin-induced resistance[56,58]
miR101Downregulated in cell lines (SMMC-7721, HepG2, Bel-4404, and 97L) and tissues, associated with distant metastasis and related to poor prognosisInhibited autophagy, by reducing STMN1, RAB5A, ATG4D and mTOR expression (involved in the phagosome formation)Sensitized HepG2 cells to apoptosis induced by cisplatin[61,62]
miR216bDownregulated in patient plasma and tissues, related to poor prognosisInhibited autophagy, by targeting . MALAT1 (an oncogenic long non-coding RNA generally upregulated in HCC that modulates chemosensitivity)Sensitized BEL-7402/5-FU resistant cells to 5-FU-, DOX- and mitomycin-induced death[65,66]
miR142-3pDownregulated in tissues, also by sorafenib treatmentInhibited sorafenib-induced autophagy by binding to the 3’-UTR of ATG5 and ATG16L1Sensitized SMCC-7721 and HepG2 cells to sorafenib-induced death[69,70]
miR21Overexpressed in patient tissues and in drug-resistant cellsInhibited autophagy, and downregulated PTEN pathwaymiR21-dependent autophagy inhibition contributed to sorafenib resistance in Huh7 and HepG2 cells and HCC tumors developed in mice[72-74]
miR423-5pOverexpressed in tissues, also elevated in serum of sorafenib-treated patients, and secreted in high levels from sorafenib-treated cellsInduced autophagyProposed as a helpful tool to predict patient response to sorafenib treatment[77,78]