Table 1 Examples of Autophagy regulation by non-coding RNAs in PCa
NcRNAs | In vitro/In vivo | PCa Cell line(s) | Patients/Animal model | Target pathway(s) | Effect on autophagy | Finding(s) | Ref. |
|---|---|---|---|---|---|---|---|
LncRNA PRRT3-AS1 | In vitro/In vivo | DU145, LNCaP, PC3, IA8 and IF11 | BALB/c- nude mice bearing PC3 xenograft | mTOR pathway | ↓ | Silencing the PRRT3-AS1 was shown to trigger the PPARγ gene, which might limit PCa cell growth while also promoting apoptotic cascade and autophagy. | [181] |
LncRNA SNHG12 | In vitro/In vivo | 22RV1, Du145, LNCaP, MDaPCa2b | Serum from PCa patients | PI3K/AKT/mTOR pathway miR-195-Cyclin E1 (CCNE1) | ↓ | SNHG12 upregulation increased cell survival and prevented apoptosis and autophagy in PCa cells through controlling CCNE1 expression via miR-195 sponging. The expression of SNHG12 was shown to be increased in PCa patients’ serum. | [183] |
LncRNA SNHG1 | In vitro/In vivo | LNCaP, PC3 and DU145 | PCa tissue sample from patients / BALB/c nude mice bearing PC3 xenograft | Targeting EZH2 Wnt/β-catenin and PI3K/AKT/mTOR pathways | ↑ | SNHG1 is abundantly expressed in PCa. and induces PCa cell proliferation, apoptosis, and autophagy. SNHG1 expression is favorably connected to PCa patient prognosis, but EZH2 expression is adversely associated with their prognosis. | [184] |
LncRNA HULC | In vitro/In vivo | DU-145, PC3, LNCaP, and RWPE-1 | NOD-SCID mice bearing PC3 xenograft with aberrant HULC expression | mTOR pathway Beclin 1 | ↓ | HULC knockdown increased PCa cell susceptibility to irradiation by boosting apoptotic cascade and autophagy while suppressing the cell cycle in vitro and in vivo. | [185] |
LncRNA PCDRlnc1 | In vitro/In vivo | PC3-DR and DU145-DR | Metastatic PCa tissue or blood samples from patients / Balb/c nude mice-bearing PC3-DR or PCDRlnc1-deleted PC3-DR xenograft | UHRF1-Beclin 1 | ↑ | PCDRlnc1 enhances autophagy and resistance to docetaxel in PCa cells by interaction with UHRF1 and boosting its transcription, increasing Beclin 1 expression. | [186] |
miR-205 | In vitro/In vivo | DU145, and PC3 | SCID mice-bearing DU145/miRVec and DU145/miR-205 xenograft | RAB27A and LAMP3 | ↓ | miR-205 is downregulated in PCa. Loss of miR-205 potentially helps PCa cells develop mesenchymal traits while establishing a favorable autophagic environment that provides a chemoresistant phenotype. Boosting miR-205 expression may be a viable strategy for overcoming platinum compounds-resistance in PCa. | [187] |
miR-34a | In vitro/In vivo | PC3 and DU145 | PCa tissue samples from patients | AMPK/mTOR-ATG4B pathway | ↓ | miR-34a is downregulated in PCa. Overexpression of miR-34a improves chemosensitivity, decreases cell proliferation, and increases apoptosis in PCa cells. | [188] |
miR-Â124 and miR-Â144 | In vitro | DU145 and PC3 | - | PIM1 | ↓ | Hypoxia causes additional downregulation of miR-124 and miR-144. Overexpression of miR-124 or miR-144 suppresses hypoxia-induced autophagy and improves radio-sensitivity. | [189] |
miR-96 | In vitro/In vivo | LNCaP and 22Rv1 | PCa tissue sample from patients / Athymic nude mice bearing LNCaP xenograft | mTOR pathway ATG7 | ↑ Biphasic ↓ | miR-96 regulates hypoxia-induced autophagy, at least to some degree. Depending on miR-96 expression levels, miR-96 can either stimulate or inhibit autophagy by primarily acting on mTOR or ATG7 pathways. Up- or down-regulation of miR-96 reduced tumor growth in vivo and PCa cell proliferation in vitro. | [190] |
miR-301a/b | In vitro | LNCaP, PC3 and DU145 | - | NDRG2 | ↑ | Hypoxia resulted in a substantial overexpression of miR-301a/b in PCa cells. miR-301a/b can specifically target the 3’UTR of NDRG2 and reduce its expression. Reduced expression of NDRG2 boosted autophagy and cell survival while decreasing apoptosis. | [191] |