MicroRNA‑485 targets MACC1 and inhibits cervical cancer cell proliferation and invasion

Abstract

A large body of evidence has indicated that microRNAs (miRNAs/miRs) have essential roles in the development and progression of cervical cancer. Thus, miRNAs with dysregulated expression are potential biomarkers for cervical cancer diagnosis and prognosis. In the present study, expression levels of miR‑485 were detected in cervical cancer tissues and cell lines. The effects of miR‑485 overexpression on the proliferation and invasion of cervical cancer cells were determined with Cell Counting kit‑8 and Transwell invasion assays. The mechanisms underlying the action of miR‑485 in cervical cancer were investigated using bioinformatics analysis, a luciferase reporter assay, reverse transcription‑quantitative polymerase chain reaction and western blot analysis. In addition, the association between miR‑485 and metastasis associated in colon cancer‑1 (MACC1) in cervical cancer tissues was examined. The present study demonstrated that miR‑485 expression was significantly downregulated in cervical cancer tissues and cell lines. Reduced miR‑485 expression in patients with cervical cancer was correlated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Furthermore, restored expression of miR‑485 significantly reduced cervical cancer cell proliferation and invasion. MACC1 was identified as a direct target gene of miR‑485 in cervical cancer. MACC1 expression was significantly upregulated in cervical cancer specimens and was inversely correlated with miR‑485 expression. Additionally, the restored expression of MACC1 eliminated the suppressive effects of miR‑485 overexpression on the proliferation and invasion of cervical cancer cells. Notably, the upregulation of miR‑485 suppressed the MET proto‑oncogene, receptor tyrosine kinase (Met)/RAC‑α serine/threonine‑protein kinase (AKT) signaling pathway. These results demonstrated that miR‑485 may perform its tumor suppressive function in cervical cancer by directly targeting MACC1 and inhibiting the Met/AKT signaling pathway. Therefore, the miR‑485/MACC1 axis may be a novel and effective therapeutic target in cervical cancer.

Prognostic and Risk Stratification Value of Lesion MACC1 Expression in Colorectal Cancer Patients

“…Authors further addressed that MACC1 overexpression favors tumor growth and promotes tumor metastasis in an athymic mice model. Multiple signal pathways such as various microRNA (29, 30), lncRNA (31, 32), circular RNA (33), and molecules such as deleted in breast cancer 1 (34), statin and rottlerin (35), have been observed in the regulation of MACC1 expression. Based on these findings, MACC1 as a potential valuable therapeutic target has been proposed.…”

The role of miRNAs in the invasion and metastasis of cervical cancer

“…With regard to the diagnosis and treatment of metastatic CC, researchers have studied cervical tissues and found a relationship between miRNAs and the diagnosis and treatment of metastatic CC. It was of interest to find that decreased miR-99a/b [90], miR-125a [139], miR-138 [75], miR-140-5p [85], miR-144 [66], miR-195 [127], miR-205 [88], miR-214 [91], miR-218 [96,133,148,167], miR-329-3p [57], miR-337 [68], miR-362 [94], miR-374c-5p [143], miR-375 [67], miR-377 [126], miR-379 [104], miR-485 [105], miR-486-3p [62], miR-638 [123], and miR-1297 [129] expression strongly correlate with tumor size, TNM stage, tissue pathology grade, International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, or distant metastasis in patients with CC. In addition, overexpressed miR-20a [31], miR-21 [168], miR-92a [118], miR-145 [79], miR-195 [166], miR-199b-5p [169], and miR-501 [51] closely correlate with histological grade, tumor diameter, overall survival (OS), progression-free survival (PFS), late FIGO stages, lymph node metastasis, or preoperative metastasis.…”

“…miR-379 might act as a tumor suppressor in CC via negatively modulating V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) [104]. miR-485, which is inversely associated with metastasis associated in colon cancer 1 (MACC1), was proven by Wang et al [105] to inhibit the invasion of CC cells. Finally, based on the miRNAs mentioned above, related signaling pathways can be seen in Figure 2.…”

The role of HPV‑induced epigenetic changes in cervical carcinogenesis (Review)

“…Downregulation of this miRNA was associated with advanced stage of the disease and lymph node metastasis. It was also found that miR-485 may exert its tumor suppressive function in cervical cancer by directly targeting MACC1 and inhibiting the Met/AKT signaling pathway ( 148 ). Conversely, downregulation of miR-664 in UCC resulted in increased expression of the c-Myc oncogene and the cyclin D gene, in-turn resulting in reduced expression of BAX and active Caspase-3.…”