PCa is the most common malignancy in males and one of the leading causes of cancer-related mortality worldwide (16). In a study investigating the underlying mechanisms of miRNAs in the development of PCa, miRNAs were found to affect the viability, migration and invasiveness of PCa cells by downregulating and potentially upregulating target genes. Cyclin B1 (CCNB1) overexpression is associated with an aggressive phenotype and functions as an independent prognostic factor in various cancers (17,18). miRNA target prediction analysis and chromatin immunoprecipitation (ChIP) assay revealed that miRNAs, including miR-744 and miR-1186, regulate the transcription of CCNB1 by interacting with distinct binding sites in the CCNB1 promoter and increasing the enrichment of RNA polymerase II (PolII) and trimethylation of histone 3 at lysine 4, thus enhancing the proliferation of PCa cells (19). However, prolonged overexpression of miR-744 and miR-1186 negatively regulates tumor growth in PCa cells as the chromosome composition is altered, consequently leading to chromosomal instability (19). Majid et al (20) reported that miR-205 inhibited PCa cell proliferation and impaired cell viability, at least in part by binding to the promoters of interleukin (IL)24 and IL32 and inducing their gene expression, as determined through sequence scanning analysis and luciferase reporter assay. Furthermore, a ChIP assay with biotinylated miRNA confirmed that miR-3619-5p enhanced cyclin-dependent kinase (CDK) inhibitor 1A transcription by interacting with its promoter, suppressing the growth of PCa cells (21). In addition, Zhang et al (22) reported that miR-1236-3p activates the expression of P21, a tumor suppressor or oncogene, by interacting with the promoter region, as determined with a sequence scanning analysis, consequently inhibiting the proliferation and metastasis of PCa cells.

BCa is the most common urinary tract malignancy and has a high incidence worldwide (23,24). Li et al (25) performed a luciferase reporter assay and revealed that miR-877-3p increased the expression of P16 by binding to its promoter and significantly suppressing the proliferation and tumorigenicity of BCa cells via inducing G1-phase arrest. This process was mediated by the inhibition of CDKs, such as CDK4 and CDK6 (26). Wang et al (27) performed a ChIP assay via biotinylated miRNAs and found that P21 was inhibited by three miRNAs (miR-370-5p, miR-1180-5p and miR-1236-3p) at diverse sites on its promoter to inhibit BCa cell migration and invasion and induce apoptosis. As a subclass of the cadherin family, epithelial cadherin (E-cadherin) has an essential role in maintaining epithelial cell-cell adhesion and intercellular junctions (28). In a ChIP assay with biotinylated miR-373, miR-373 was revealed to facilitate E-cadherin expression by interacting with its gene promoter, with the effect of inhibiting BCa cell proliferation (29). Taken together, these findings support the development of novel therapies based on potentially targeted genes for BCa.

RCC is a common kidney cancer and the most frequent renal neoplasm (30,31). Wang et al (32) investigated the mechanisms underlying the role of miR-1236-3p in RCC progression and found that miR-1236-3p directly targets the P21 promoter to regulate its gene expression by using a ChIP assay with biotinylated miR-1236-3p, with the ultimate effect to inhibit its function and leading to the suppression of RCC cell proliferation. The result of a luciferase reporter assay showed that miR-24-1 overexpression enhanced fructose-1,6-bisphosphatase transcription by increasing its enhancer activity to attenuate RCC proliferation and metastasis (33).

WT is the most common pediatric renal tumor and is associated with nephrogenesis, which may lead to malformations or overgrowth (34). Liu et al (35) showed that nuclear miR-483, which is overexpressed in WT, enhanced insulin-like growth factor 2 (IGF2) transcription through interaction with the 5′-UTR of IGF2, as indicated using a biotinylated miRNA-RNA affinity pulldown assay.

BC is one of the most lethal and widespread cancers among females worldwide. It occurs in the epithelial tissue of the mammary gland and comprises diverse morphological characteristics (36,37). In three studies on the role of miRNAs in human BC, the authors performed a luciferase assay to investigate the roles of nuclear miRNAs in gene transcription. Tan et al (38) revealed that miRNA-10a mediates the repression of target promoters on homeobox D4 by interfering with promoter-associated transcripts to impact the development of BC. Liang et al (39) demonstrated that miR-339 represses the proliferation of BC cells, leading to the upregulation of tumor suppressor gene G protein-coupled estrogen receptor 1 expression by enhancer switching, indicating that miR-339 is a potential target and novel approach for the treatment of BC, particularly for triple-negative BC. In addition, Seviour et al (40) verified that, by binding to the P27 promoter, miR-124 induced the transcription of the P27 gene, leading to a subsequent G1-phase arrest. As a tumor suppressor, miR-124 was able to impair the growth of BC and OC cells and sensitize cells to etoposide.

OC is associated with the highest mortality rate among gynecological malignancies (41). Forkhead box (Fox)o3 regulates ovarian follicular development and atresia (42). A luciferase reporter assay and a ChIP assay indicated that the interaction between miR-195-5p and the Foxo3 promoter may be associated with AGO2 recruitment and histone modification, which affect follicular development (43). In addition, Chaluvally-Raghavan et al (44) found that miR-551b-3p interacted directly with a complementary sequence within the signal transducer and activator 3 (STAT3) promoter by recruiting PolII, thus facilitating STAT3 transcription. By contrast, silencing miR-551b-3p inhibited the growth of OC cells, as shown using luciferase reporter and DNA pull-down assays.

Gliomas account for the majority of primary malignant and central nervous system tumors and are associated with high morbidity and mortality (45,46). Wang et al (47) reported that miR-215-5p increases the development of aggressive phenotypes, facilitates cell proliferation and migration, and represses apoptosis in gliomas at least in part by negatively regulating the expression of protocadherin 9 via targeting both its promoter and 3′-UTR, as determined by sequence scanning analysis and a luciferase reporter assay.

NB is a common extracranial solid tumor in children, mostly under the age of 10 years (48), and is an embryonal neoplasm of the sympathetic nervous system (49,50). NB exhibits clinical heterogeneity in response to current monotherapies (51,52). Researchers have studied the mechanisms underlying the role of miRNAs in NB. Luciferase reporter and ChIP assays demonstrated that miR-584-5p (53) and miR-337-3p (54) are involved in repressing the transcription of matrix metalloproteinase (MMP-14) by binding to different binding sites of its promoter, recruiting AGO2 and attenuating the proliferation, invasion, metastasis and angiogenesis of NB (55). By contrast, using a sequence scanning analysis and luciferase reporter assay, Qu et al (56) found that miR-558 facilitates the transcription of heparinase (HPSE) by binding to the MMP-14 promoter, recruiting AGO1 to promote the proliferation, invasion, metastasis and angiogenesis of NB.

Colon cancer is a malignant tumor and a common cause of cancer-related death worldwide, which may spread to organs such as the lymph nodes, liver, lungs and ovaries (57). P21 is a CDK inhibitor that is frequently deregulated in cancers, depending on the cellular context (58). Kang et al (59) performed a ChIP assay and found that miR-6734 induced the transcription of P21 and attenuated the proliferation and survival of HCT-116 cells by facilitating cell cycle arrest and apoptosis.

GC is a heterogeneous disease and the fifth most common cancer type worldwide (37). The pathogenesis of GC is multifactorial and is associated with smoking and Helicobacter pylori infection (60). MMP-14 has a pivotal role in activating MMP-2 and is elevated in most human cancers, including GC (61), where it promotes tumor invasion and metastasis (62). A luciferase reporter assay indicated that miR-337-3p interacts directly with the MMP-14 promoter within the -90 to -71 bp region to repress myeloid zinc finger 1-facilitated MMP-14 expression through inducing repressive chromatin remodeling and recruiting AGO2, thus suppressing the growth, metastasis, invasion and angiogenesis of GC cells (63).

HPSE is amplified and overexpressed in GC specimens (64). HSPE exerts a crucial role in extracellular matrix degradation, facilitating the growth, invasiveness, metastasis and angiogenesis of tumors (65). Luciferase reporter and ChIP assays found that miR-558, which is upregulated in GC, targets the complementary site within the HPSE promoter to induce its expression, facilitating GC progression, metastasis and angiogenesis (66).

Lung cancer is the leading cause of cancer-related morbidity and mortality in China, and NSCLC accounts for the overwhelming majority of lung cancer cases (67). miR-1236-3p and miR-370-5p negatively regulate the proliferation, migration and invasiveness of NSCLC cells at least in part by targeting the promoter of the P21 gene to upregulate its expression, as indicated using sequence scanning analysis (68). As a major component of the activator protein-1 complex, c-Fos has been implicated in cell differentiation, proliferation, motility, cancer growth, angiogenesis, invasion and metastasis (69). The results of a luciferase reporter assay indicated that miR-744 acts as an oncogene in NSCLC cell growth and metastasis at least in part by directly binding to the promoter of c-Fos (70). Li et al (71) found that miR-26A1 is decreased in NSCLC and used luciferase reporter and ChIP assays to demonstrate that miR-26A1 acts as a key regulator in reactivating villin 1-like protein by targeting its enhancer, leading to the inhibition of the proliferation and metastasis of NSCLC cells.

NPC is a malignant tumor associated with a specific geographical distribution in Southeast Asia and North Africa (72,73). Rho GTPase activating protein 5 (ARHGAP5), a proto-oncogene, is a direct target of miR-744. Using a luciferase reporter assay, Fang et al (74) found that miR-744 facilitates expression at the transcriptional level by directly targeting the ARHGAP5 promoter, consequently enhancing the progression and metastasis of NPC.