Abstract

Objective To investigate the expression and regulation mechanism of miR-29c-3p and cell division cycle associated 4 (CDCA4) in melanoma (MM). Data and Methods. Fifty-nine patients with MM admitted to our hospital were enrolled as the MM group. They were followed up for 3 years to analyze the prognostic factors; meanwhile, 51 healthy subjects were allocated into a normal group. MM cell lines (M21 and C8161) were transfected with miR-29c-3p-mimics, miR-29c-3p-inhibitor, miR-NC, si-CDCA4, and sh-CDCA4. The expression of miR-29c-3p, CDCA4, Bax, Caspase3, Bcl-2, N-cadherin, vimentin, and E-cadherin was quantified, and cell proliferation, migration, invasion, and apoptosis, as well as epithelial-mesenchymal transition (EMT), were determined. Results Serum miR-29c-3p was lowly expressed and CDCA4 was highly expressed in the MM group. The area under the curve (AUC) of both for diagnosing MM was greater than 0.9. miR-29c-3p and CDCA4 were related to regional lymph node staging (N staging), distant metastasis (M staging), tumor diameter, and pathological differentiation. Low miR-29c-3p and high CDCA4 were associated with poor prognosis of MM. Overexpression of miR-29c-3p and suppression of CDCA4 hindered cell proliferation, migration, invasion, and expression of Bax, Caspase3, N-cadherin, and vimentin, but cell apoptosis and expression of Bcl-2 and E-cadherin were enhanced. Dual-luciferase reporter (DLR) assay confirmed the targeted relationship between miR-29c-3p and CDCA4. After miR-29c-3p-mimics+sh-CDCA4 was transfected into M21 and C8161 cells, the proliferation, invasion, and apoptosis were not different from those in the miR-NC group transfected with unrelated sequences. Conclusion Overexpression of miR-29c-3p suppresses CDCA4 expression and decreases proliferation, migration, invasion, apoptosis, and EMT of MM cells, thus hindering MM progression.

Highlights

  • Melanoma (MM) is a prevalent malignant tumor in western countries with a highly heterogeneous prognosis in advanced patients and a rising incidence [1, 2]

  • Pearson’s test revealed the negative correlation between the expressions of miR-29c-3p and cell division cycle associated 4 (CDCA4) (r = −0:671, P < 0:001). Both miR-29c-3p and CDCA4 were associated with regional lymph node staging (N staging), distant metastasis (M staging), tumor diameter, and pathological differentiation (P < 0:05), and miR-29c-3p is closely correlated with tumor invasion staging (T staging) (P < 0:05)

  • We found that miR-29c-3p hinders the progression of MM through the targeted inhibition of CDCA4

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Summary

Introduction

Melanoma (MM) is a prevalent malignant tumor in western countries with a highly heterogeneous prognosis in advanced patients and a rising incidence [1, 2]. Resection operation is the preferred choice for early-stage patients, and interferon-α- (INF-α-) based adjuvant therapy and systemic therapy were generally applied to middle- and advancedstage patients, respectively. Those treatment regimens are more or less potentially dangerous [5]. Progression to advanced MM leads to greatly reduced therapeutic effectiveness and high cost, and the best way to prevent the progression is early diagnosis [6]. It is of great significance to find reliable, convenient, and cost-effective biological diagnostic indicators for prevention, early diagnosis, and treatment of MM

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