Table 3.

Examples of the mechanisms of miRNA-mediated resistance in ovarian cancer.

References	miRNA	Expression in resistant cells	Target gene	Suggested mechanism
Xu et al. (148)	miR-497	Down	mTOR/P70S6K1	The resultant activation of mTOR/P70S6K1 positively affects several downstream effectors to regulate cell growth, proliferation, and survival (149).
Chen et al. (150)	miR-133b	Down	GST-π	GSTs have the ability to detoxify cytostatic drugs (151). Therefore, chemotherapy-resistant ovarian cancer cells might develop resistance by upregulating the miR-133b-target gene GST-π.
van Jaarsveld et al. (152)	miR-634	Down	CCND1, GRB2, ERK2, and RSK2	Upregulation and activation of these MAPK pathway components produce undesirable effects on several fundamental cellular processes, including cell cycle progression and inhibition of apoptosis (153).
Dwivedi et al. (154)	miR-15a miR-16	Down	BMI1	Bmi1, a member of the Polycomb Repressor Complex 1, is a crucial regulator of the self-renewal and malignant transformation of many cancers (see Table 2).
Cui et al. (155)	miR-146a	Down	SOD2	Resistant cells have shown higher levels of the antioxidant SOD2, which scavenge any reactive species produced by the chemotherapy and thus resist death (156).
Guo et al. (157)	miR-100	Down	mTOR and PLK1	Cells are able to develop resistance by enhancing the functions of the mitotic regulator gene Polo-like kinase 1 (Plk1) (158), in addition to the other oncogenic roles of mTOR (see above).
Zhu et al. (159)	miR-186	Down	Twist1	Twist1 can confer chemoresistance in different cancers by regulating several downstream signaling proteins, including mTOR and Bcl2. In addition, Twist1 binds and activates ABC transporters, mediates EMT-induced resistance, and positively regulates PI3K/AKT pathway (160).
Han et al. (161)	miR-30a/c-5p	Down	Snail	DNMT1-mediated silencing of miR-30a/c-5p upregulates E-cadherin-transcriptional repressor Snail, thereby promoting EMT-mediated resistance to cisplatin.
Vera et al. (162)	miR-7	Down	MAFG	Recent evidence suggests that MAFG confers antioxidant activity against free radicals produced as a result of cisplatin treatment, which might be the mechanism behind MAFG-induced cisplatin resistance (163).
Jiang et al. (164)	miR-139-5p	Down	C-Jun	The resultant overexpression of the proto-oncogene c-Jun promotes the expression of the anti-apoptotic protein Bcl-XL, thereby suppressing the apoptotic death of these cells.
Kanlikilicer et al. (165)	miR-1246	Up	Cav1	Upregulated miR-1246 potentiates resistance toward paclitaxel through the downregulation of Cav1, a protein that directly binds and inhibits the kinase activity of the platelet-derived growth factor receptor PDGFRβ, which correlates with induction of the p-glycoprotein (MDR1) levels.
Chen et al. (166)	miR-139-5p	Down	RNF2	Evidence suggests that ovarian cancer cells can develop resistance by upregulating the ring finger protein 2, RNF2, an E3 ligase that targets the tumor suppressor p53 for degradation, thereby inhibiting cellular apoptosis (167).
Zhang et al. (168)	miR-1294	Down	IGF1R	See Table 2
Xu et al. (169)	miR-378a-3p	Down	MAPK1/GRB2	See above
Jiang et al. (170)	miR-383-5p	Down	TRIM27	See above
Sun et al. (171)	miR-137	Down	EZH2	EZH2 functions as a transcriptional suppressor or a transcriptional co-activator through epigenetic regulation of histone methylation. Evidence has shown that the upregulation of EZH2 strongly correlates with cisplatin resistance (172, 173).
Park and Kim (174)	miR-503-5p	Down	CD97	CD97 is a member of the epidermal growth factor (EGF)-seven transmembrane family that signals through Janus-activated kinase 2(JAK2), a signal transducer and activator of transcription 3 (STAT3), to induce paclitaxel resistance in ovarian carcinoma.
Nakamura et al. (175)	miR-194-5p	Down	MDM2	Upregulation of the E3 ubiquitin ligase, MDM2, blocks the transcriptional activity of several tumor suppressor genes, including p53 and p21.
Li et al. (176)	miR-142-5p	Down	XIAP	See Table 2.
Zhang et al. (177)	miR-574-3p	Down	EGFR	Cells might confer resistance toward chemotherapies by activating several signaling cascades involved in proliferation and survival that are downstream of the oncogenic EGFR (178).
Dai et al. (179)	miR-195-5p	Down	PSAT1	PSAT1-promotes inactivating phosphorylation of GSK3β, allowing the accumulation and nuclear translocation of β-catenin, which might help in conferring resistance by upregulating the stress-related gene, HIF-1α.