Retracted: MicroRNA‐497 accelerates apoptosis while inhibiting proliferation, migration, and invasion through negative regulation of the MAPK/ERK signaling pathway via RAF‐1

Abstract

The aim of this study is to explore the various modes of action miR-497 has on human cervical cancer (CC) cell behavior. We also speculate that miR-497 achieves its anti-tumor role by governing RAF-1 via MAPK/ERK signaling pathway. CC tissues with corresponding adjacent normal tissues were collected from 168 CC patients. RAF-1-positive cells were identified by means of immunohistochemistry in tissues. A series of inhibitors, mimics and siRNA against RAF-1 were introduced to validate regulatory mechanisms for miR-497 and RAF-1. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assay were employed for evaluating alternations of miR-497, RAF-1, and MAPK/ERK signaling pathway. HeLa cell proliferation, invasion, migration, cycle progression, and apoptosis were assessed by means of CCK-8, wound-healing, transwell invasion assays, and flow cytometry, respectively. The target prediction program and luciferase activity determination were used to identify miR-497 targeting RAF-1. We determined reduced miR-497 expression and elevated expression of RAF-1 in CC tissues as opposed to adjacent tissues. Transfection of miR-497 mimics and siRNA-RAF-1 both decreased levels of MEK1, ERK1, and p38 phosphorylation in HeLa cells, inhibited cell proliferation, migration and invasion, induced more cells arrested in the G0/G1 phase, and promoted cell apoptosis; while miR-497 inhibitors led to opposite results. These findings indicate miR-497 as a tumor suppressor results from negative regulation of the MAPK/ERK signaling pathway via RAF-1 in CC.

RAF1 as Downstream Molecule Mediates the FSH Signaling Pathway to Stimulate E2 Synthesis and Secretion in Mouse Ovarian Granulosa Cells

“…Many studies suggested that RAF can affect the proliferation of cell through in uencing the distribution of cell cycle [29][30][31], and we speculated that the signi cant and rapid change of estradiol level was caused by GCs proliferation. Our ow cytometry analysis results showed that RAF709 did not induce the suppression of cell cycle stage, but affected on the activity of estradiol synthase, which con rmed that RAF1 could regulate the expression of CYP19A1 [32] through the ERK signaling pathways [33]. Besides, our results showed that RAF1 regulated CYP19A1 by the phosphorylation of ERK, which is consistent with the ndings that RAF-ERK pathway played a vital role in mediated steroidogenesis [28].…”

Anti-Cancer Effects of Pristimerin and the Mechanisms: A Critical Review

“…The generic MAPK signaling pathway is co-regulated by four different cascades including extracellular signal-related kinases (ERK1/2), Jun amino-terminal kinases (JNK1/2/3), p38-MAPK, and ERK5 (Sun et al, 2015). MAPK/ERK pathway regulates the cell proliferation (Sun et al, 2017), differentiation (Wang et al, 2017), migration (Tao et al, 2018) and apoptosis (Wang and Zhu, 2018).…”

MicroRNA-497-5p inhibits proliferation and invasion of non-small cell lung cancer by regulating FGF2

“…Wu et al (12) proposed that miR-497 inhibited proliferation and induced apoptosis via the Bcl-2/Bax-caspase-9-caspase-3 pathway in HUVECs. It was also reported that miR-497 accelerated apoptosis of cervical cancer cells through negatively regulating the MAPK/ERK signaling pathway (13). However, it has been reported that miR-497 can also express high and enhanced metastasis by inhibiting SMAD7 in oral squamous cell carcinoma (14).…”