miR‑186 promotes tumor growth in cutaneous squamous cell carcinoma by inhibiting apoptotic protease activating factor‑1

Abstract

Cutaneous squamous cell carcinoma (cSCC) accounts for 20% of non-melanoma skin cancer worldwide. MicroRNAs (miRNAs or miRs) are a subtype of non-coding RNA associated with the progression of various types of human cancer. MiR-186 has been demonstrated to act as an oncogene in human tumors. However, the role of miR-186 in cSCC remains unclear. The expression of miR-186 and apoptotic protease activating factor 1 (APAF1) was examined using reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence. The correlation between miR-186 and APAF1 was determined using a dual-luciferase assay. Mimics or inhibitors of miR-186 were transfected into A-431 cells to establish cell lines with overexpressed or knocked-down miR-186, respectively. EdU staining and colony formation assays were performed to detect cell proliferation. Transwell and wound-healing assays were performed to analyze cell invasion and migration, respectively. Hoechst staining and flow cytometry were performed to assess cell apoptosis and cell cycle distribution. MiR-186 expression was significantly increased, while APAF1 expression was significantly decreased in cSCC tissues compared with the controls. An miR-186 binding site was predicted in APAF1 and their expression was negatively correlated in cSCC tissues. Cell proliferation, invasion and migration were significantly enhanced in the miR-186-overexpressed A-431 cells and attenuated in miR-186 knockdown cells compared with the control. APAF1 expression was regulated by miR-186, while APAF1 knockdown significantly promoted cell invasion and inhibited cell apoptosis. In summary, the results of the present study indicate that miR-186 serves as an oncogene in cSCC by inhibiting APAF1.

Silencing circular RNA circZNF609 restrains growth, migration and invasion by up-regulating microRNA-186-5p in prostate cancer

“…Many researchers had put forward that miR-186 conspicuously restrained the occurrence of tumour. For instance, Tian et al had verified that miR-186 restrained squamous cell tumour [23] and Hua et al had verified that miR-186 restrained PC cell viability [24]. In addition, Jones et al had verified that miR-186-5p restrained PC [17].…”

The Dual Role of miR-186 in Cancers: Oncomir Battling With Tumor Suppressor miRNA

“…APAF1, a critical component of the apoptosome to promote endogenous apoptotic process, was verified to be a functional target of miR-186 in tissues and cells of squamous cell carcinoma (cSCC). Enforced overexpression of miR-186 in cSCC cells significantly increased cell growth, invasion, and migration, and apoptosis was significantly increased when miR-186 expression was inhibited (11). RETREG1, also known as FAM134B, was another target of miR-186 in increasing proliferation and inhibiting apoptosis in cSCC.…”

Deciphering the Molecular Landscape of Cutaneous Squamous Cell Carcinoma for Better Diagnosis and Treatment

“…Upregulation of miR-205 also induced cancerous keratinocyte proliferation and migration by targeting lipid phosphatase SHIP2 [ 98 , 99 ]. In the same cell line, miR-186 targets APAF1, a key molecule in the intrinsic apoptosis pathway [ 100 ]. In response to cytochrome c release, APAF1 oligomerizes and forms the apoptosome [ 101 ], therefore, its downregulation as a consequence of miR-186 overexpression inhibits tumor cell apoptosis and promotes cSCC proliferation, invasion and migration [ 100 ].…”