ALOX12B promotes carcinogenesis in cervical cancer by regulating the PI3K/ERK1 signaling pathway

Abstract

Cervical cancer is a malignant disease and a threat to women's health worldwide. Surgical resection followed by radiotherapy or chemotherapy is the main treatment strategy for cervical cancer; however, patients with cervical cancer, especially those with late-stage disease, may not benefit from these traditional therapies, which results in poor clinical outcome. ALOX12B is a gene encoding lipoxygenase, and a mutation in ALOX12B was detected in lung and breast cancer. Furthermore, ALOX12B is essential to the proliferation of epidermoid carcinoma cells; however, the role of ALOX12B in cervical cancer has not been studied thus far, to the best of our knowledge. In the present study, the expression levels of ALOX12B were reduced in cervical cancer cells by lentiviral transfection, and it was found that both cell proliferation and clone formation ability were significantly reduced, and the cell cycle was blocked at G 1 phase. Tumor growth was also suppressed in vivo in a xenograft tumor model, but the migration of tumor cells was not affected by ALOX12B. Subsequently, using western blotting, it was demonstrated that knockdown of ALOX12B decreased the expression levels of PI3K, MEK1, ERK1, C-fos and cdc25. Meanwhile, overexpression of ALOX12B increased the expression levels of these five molecules. Conclusively, ALOX12B promoted cell proliferation in cervical cancer via regulation of the PI3K/ERK1 signaling pathway. The present study may improve our understanding of the molecular mechanisms underlying the function of ALOX12B in cervical cancer and inform new therapeutic strategies.

Ferroptosis-Related Genes in Lung Adenocarcinoma: Prognostic Signature and Immune, Drug Resistance, Mutation Analysis

“…ALOX12B, R-type of ALOX12 catalyzed by ALOX12, is necessary for p53-mediated antitumor effect via ferroptosis ( Mashima and Okuyama, 2015 ). Jiang et al (2020) have demonstrated that ALOX12B promotes cervical cancer progression through modulating the PI3K/ERK1 signaling pathway. ALOX12B has a negative relation to the prognosis of LUAD in our study, which indicates that ALOX12B may be involved in some other tumor regulatory mechanisms ( Jiang et al, 2020 ).…”

A Novel Ferroptosis-Related Biomarker Signature to Predict Overall Survival of Esophageal Squamous Cell Carcinoma

“…ALOX12B protein, another isoform of arachidonic acid 12-lipoxygenase, mainly catalyzes arachidonic acid to 12R-hydroxyeicosatetraenoic acid ( Zheng et al, 2011 ). Jiang et al revealed that the inhibition of ALOX12B could restrain cervical cancer cell proliferation and growth through suppressing the PI3K/ERK1 pathway, suggesting that it can be taken as a good biomarker to provide new therapeutic strategies for cervical cancer patients ( Jiang et al, 2020 ). In addition, Chu et al reported that ALOX12 could oxygenate polyunsaturated fatty acids, which in turn induce p53-mediated tumor cell ferroptosis ( Chu et al, 2019 ).…”

Prediction and prognostic significance of ALOX12B and PACSIN1 expression in gastric cancer by genome-wide RNA expression and methylation analysis

“…Low expression levels of ALOX12B were found to significantly reduce both cell proliferation and clone formation ability, and block cell cycle at G1 phase in cervical cancer. Tumor growth was also suppressed in vivo in a xenograft tumor model (33). Studies associating PACSIN1 have revealed that it works as a critical regulator of synaptic inhibition (30), regulator for tolllike receptor (TLR)7/9 interferon response (34), for axonal elongation and branching (35), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) receptor trafficking (36).…”