miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6

Abstract

Background: The aberrant expression of microRNA-454 (miR-454) has been confirmed to be involved in the development of cancers. However, the functional role of miR-454 in the progression of ovarian cancer remains unclear. Methods: The expression of miR-454 in ovarian cancer cells and serum of ovarian cancer patients was detected by RT-PCR. CCK8, colony formation, transwell, and flow cytometry assays were conducted to assess the effects of miR-454 on ovarian cancer cell proliferation, migration, invasion, and apoptosis, respectively. Dual-luciferase reporter assay was used to confirm the targeting relationship between miR-454 and E2F6. The expression pattern of E2F6 in ovarian cancer tissues was detected using immunohistochemistry (IHC) assay. The relative expression of related proteins was examined using western blot analysis. Results: miR-454 was markedly down-regulated by hypoxia in ovarian cancer cells. Compared with normal samples, the expression of miR-454 was up-regulated in the serum of ovarian cancer patients, and correlated with the clinicopathological stages of ovarian cancer. Next, we found that miR-454 overexpression inhibited the proliferation, migration and invasion of OVCAR3 and SKOV3 cells, as well as promoted apoptosis. In addition, the Akt/mTOR and Wnt/βcatenin signaling pathway were inhibited by miR-454 in ovarian cancer cells. Mechanically, bioinformatic analysis and dual-luciferase reporter assay confirmed that E2F6 was a direct target of miR-454 and negatively regulated by miR-454 in ovarian cancer cells. Moreover, IHC analysis showed that E2F6 was highly expressed in ovarian cancer tissues. Finally, we found that the increasing cell proliferation and migration triggered by E2F6 overexpression were abolished by miR-454 overexpression. Conclusion: Taken together, these results highlight the role of miR-454 as a tumor suppressor in ovarian cancer cells by targeting E2F6, indicating that miR-454 may be a potential diagnostic biomarker and therapeutic target for ovarian cancer.

Long noncoding RNA SLC9A3‑AS1 increases E2F6 expression by sponging microRNA‑486‑5p and thus facilitates the oncogenesis of nasopharyngeal carcinoma

“…Furthermore, E2F6, a member of the nuclear transcription factor E2F family, served as a crucial mediator of miR-486-5p action in NPC. E2F6 is regulated by multiple miRNAs in human cancer ( 41 – 43 ), and the present study identified a similar trend for E2F6 in NPC. Notably, the final rescue experiments revealed that the modulatory activities of SLC9A3-AS1 silencing on NPC cells could be reversed by miR-486-5p downregulation or E2F6 reintroduction.…”

Construction and Comparison of ceRNA Regulatory Network for Different Age Female Breast Cancer

“…After consulting the relevant documents, we found that hsa-mir-454 played a non-negligible role in the development and prognosis of multiple tumor. For example, miR-454 restrained the growth and invasion of ovarian cancer cells via regulating E2F6 (An et al, 2020). The miR-454-3p may be a meaningfully standalone prognosis marker for hepatocellular carcinoma (Li et al, 2019).…”

Deciphering sex-specific miRNAs as heat-recorders in zebrafish

“…Strikingly, most of the miRNAs here identified as heat recorders, are related to ovarian and prostate cancer in humans, either promoting or suppressing cancer progression and thus much literature related to these diseases is available. This is the case of, for example, miR-19b [56], miR-15b [57], and miR-454 [58,59] three upregulated miRNAs in the fish ovaries after the heat and; miR-27b [60,61], miR-212 [62], miR-146b [63], and miR-34a [64], which were downregulated. The emerging research on miRNAs has flourished the utility of miRNAs as bioclinical markers in human cancers during the last decade [65,66] but also as attractive drug targets for human diseases with no current effective treatments [67,68].…”