nt cells in comparison with chemosensitive cancers cells. Overexpression of EZH2 initiates all round phosphorylation of kinases in serine and tyrosine residues, thereby major to chemoresistance. Nevertheless, the inhibition of EZH2 by KMTi inhibitor, EPZ011989, shown to lessen phosphorylation and activate tumor suppressors to reverse chemoresistance [30]. Not too long ago, various combinations of KMTi have already been shown to reverse back the chemoresistance of chemotherapeutics [31]. As an example, 3-deazaneplanocin A, an EZH2 inhibitor, combined with panobinostat, a HDAC inhibitor, has been shown to minimize chemoresistance in chemoresistant glioblastoma cells [32]. Related to DNA methylation and histone modification, ncRNAs, especially miRNAs, play a dynamic role in cancer chemoresistance [29]. 3. Role of miRNA in cancer chemoresistance RGS4 list miRNAs play a important part in many biological processes for example cell cycle, cell proliferation, metastasis, and cell signaling pathways [33]. Dysregulation of miRNAs may cause aberration to differentphysiological functions. Alteration inside the expression of miRNAs can improve or deteriorate the chemotherapeutic response. In addition, miRNAs regulate chemoresistance by altering the expression of tumor-suppressor genes, tumor-promoter genes, and oncogenes. miRNAs can reverse the chemosensitivity by limiting the gene expression involved in autophagy, cell survival, and DNA repair mechanisms, thereby altering cell survival, as depicted in Fig. 3. The downregulation of REV3-like DNA-directed polymerase zeta catalytic subunit (REV3L) or the upregulation of miR-29a inhibits the cell growth by arresting within the G2/M phase when co-treated with cisplatin [34]. REV3L is accountable for translation DNA synthesis. DNA repair pathway is a different mechanism involved in chemoresistance. Flap endonuclease 1 (FEN1) is involved in chemoresistance by regulating several factors involved in DNA repair pathways. Tumor suppressor miR-140 reduced the DNA repair mechanism by complementing FEN1 at 3 untranslated region3 (UTR). Therefore, upregulation of miR-140 reverses the chemosensitivity to breast cancer cells by targeting FEN1. In addition, transcription factor/repressor Ying Yang 1 (YY1) directly binds towards the miR-140 promoter and triggers miR-140 expression, decreasing doxorubicin resistance [35]. miRNAs can regulate chemoresistance by altering the expression of distinctive transcription elements linked with Epithelial-Mesenchymal Transition (EMT) [36,37]. Tumor suppressor miR-218 has an inverse correlation with ‘master switch’ runt-related transcription element 2 (RUNX2), which controls many genes involved within the development of osteoblasts. The other function of RUNX2 will be to modulate angiogenesis via cell proliferation, invasion, and angiogenesis. The overexpression of miR-218 increases cisplatin sensitivity by the downregulation of RUNX2 and enhances apoptosis and cell cycle arrest in the G0/S phase in NSCLC [38]. miR-218 can also be inversely correlated with EMT transcription aspects which include Slug and ZEB2. The upregulation of miR-218 RelB Storage & Stability augments the chemosensitivity of cells to cisplatin as well as obstructs cell migration and invasion through suppression of Slug and ZEB2 expression by blocking the 3 -UTR regions of Slug and ZEB2 [39]. miRNAs regulate different signaling pathways linked with chemoresistance mechanisms. For instance, downregulation of miR-499a inhibits cell proliferation, induces cell cycle arrest, reduces colony formation, metastas