Fig. 3

Roles of miRNAs in modulating the autophagy process in human breast cancer. MiR-486-5p is said to downregulate PTEN and this activates PI3K/Akt signaling pathway to inhibit autophagy activity [56]. An in vitro study reported eighteen miRNAs were involved in downregulating the signaling hub which covers ULK1 and these miRNA include miR-30c-1, miR-149, miR-611, miR-615-5p, miR-659, miR-636, miR-638, miR-659, miR-675, miR-1303, miR-1308, miR-1908, miR-1914, miR-1915, miR-2861, miR-3184, miR-4292 and miR-4259 [67]. This group of miRNAs was also found to downregulate the signalling hub which involves Beclin-1 by inhibiting the MAPK/JNK1 signalling pathway [67]. Another five miRNAs were reported to inhibit the ULK kinase complex and these include miR-20a and miR-20b [72], miR-25 [68], miR-489 [37] and miR-1275 [69]. On the other hand, Beclin-1 expression was found to be negatively correlated to the expression of miR-20a [74], miR-21 [75] and miR-221 [76]. MiR-20a could also suppress ATG16L1 expression [74] while miR-567 and miR-638 could negatively regulate ATG5 expression [78, 79]. Overexpression of miR-101 was linked to ATG4 downregulation [80] whereas upregulation of miR-1275 was related to ATG7 suppression [69], and both ATG4 and ATG7 are important in the LC3-II production [16]. Other miRNAs which were involved in suppressing cellular LC3-II production include miR-21 [75], miR-27a [82] and miR-96-5p [83] while miR-638 was found to be involved in promoting LC3-II production [81]. Four miRNAs were reported to be involved in suppressing SQSTM1/p62 expression and these miRNAs include miR-20a [74], miR-27a [82], miR-96-5p [83] and miR-638 [81]