Effects of microRNA-374 on proliferation, migration, invasion, and apoptosis of human SCC cells by targeting Gadd45a through P53 signaling pathway

Abstract

Correspondence: or Bao-Guo Liu (liubaoguolbg@yeah.net) The present study investigated the effects of microRNA-374 (miR-374) on human squamous cell carcinoma (SCC) cell proliferation, migration, invasion, and apoptosis through P53 signaling pathway by targeting growth arrest and DNA-damage-inducible protein 45 α (Gadd45a). Skin samples were collected from patients with skin SCC and normal skin samples. Expression of miR-374, Gadd45a, P53, P73, P16, c-myc, bcl-2, Bax, caspase-3, and caspase-9 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. A431 and SCL-1 cells were divided into blank, negative control (NC), miR-374 mimics, miR374 inhibitors, siRNA-Gadd45a, and miR-374 inhibitors + siRNA-Gadd45a groups. Their proliferation, migration, invasion, cell cycle, and apoptosis were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, scratch test, Transwell assay, and flow cytometry. SCC skin tissues exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased levels of Gadd45a, P53, c-myc, and Bcl-2 compared with the normal skin tissues. The miR-374 inhibitors group exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased expression of Gadd45a, P53, c-myc, and Bcl-2, enhanced cell proliferation, migration, and invasion, and reduced apoptosis compared with the blank and NC groups; the miR-374 mimics group followed opposite trends. Compared with the blank and NC groups, the miR-374 inhibitors + siRNA-Gadd45a group showed decreased miR-374 level; the siRNA-Gadd45a group showed elevated levels of P73, P16, Bax, caspase-3 and caspase-9, decreased levels of Gadd45a, P53, c-myc, and Bcl-2, reduced cell proliferation, migration, and invasion, and accelerated apoptosis. miR-374 induces apoptosis and inhibits proliferation, migration, and invasion of SCC cells through P53 signaling pathway by down-regulating Gadd45a.

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1

“…Moreover, the repression of DNMT1 by CH-5 could be reduced by overexpression of Sp1. Gadd45a gene is a DNA damage-inducible gene that participates in p53-dependent apoptosis [ 47 ] and is upregulated by activated p53 [ 48 ]. The expression of Gadd45a could be induced in p53 wild-type HCT116 cells treated with CH-5, but not in p53-null HCT116 cells.…”

The latest progress on miR‐374 and its functional implications in physiological and pathological processes

“…Regarding skin cancer, Ning et al revealed that miR‐374c expression was down‐regulated by next‐generation sequencing and RT‐qPCR assay in Merkel cell carcinoma and other cutaneous tumors compared with normal skin. In 2017, Li et al observed that miR‐374a expression was decreased in skin tissues of human squamous cell carcinoma compared to the normal skin tissue. Meanwhile, they verified through transfection of miR‐374 mimics into A431 and SCL‐1 cells, that miR‐374a down‐regulated the P53 signaling pathway to induce cell apoptosis and inhibit proliferation, migration and invasion by targeting its downstream protein, Gadd45a.…”

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“…43 Li et al reported that microRNA-374 affected the proliferation, migration, invasion and apoptosis of cSCC cells by targeting Gadd45a through the p53 signaling pathway. 44 However, the mechanism of wogonoside on cSCC has not been clarified. We found that phosphorylation of AKT and βcatenin was significantly reduced by wogonoside treatment, while it had little effect on STAT3 and p65.…”