The TNF‐α‐induced expression of miR‐130b protects cervical cancer cells from the cytotoxicity of TNF‐α

Abstract

Tumour necrosis factor alpha (TNF‐α) is a multifunctional cytokine and has the capacity both to promote cell growth and to kill tumour cells by inducing cell apoptosis. However, many tumour cells develop resistance to the toxic effects of TNF‐α. Thus, understanding the mechanism underlying the resistance of tumours to TNF‐α toxicity and finding ways to overcome this resistance are urgently needed. In this study, we discovered that two cervical cancer cell lines, Hela and Siha, showed null responses to TNF‐α cytotoxicity. However, in these cell lines, TNF‐α stimulation promoted the expression of miR‐130b and downregulated the expression of PTEN gene, which encodes a dual‐specificity phosphatase that acts as a tumour suppressor. Blockade of miR‐130b function or overexpression of PTEN gene sensitized cells to TNF‐α cytotoxicity. Regression analyses revealed that there were reverse relationships between the cellular levels of miR‐130b and PTEN mRNA in cervical cancer cells. Gain‐ and loss‐of‐function assays demonstrated that there were causal relationships between the increase in miR‐130b levels and the reduction in PTEN mRNA or PTEN protein levels. In silico analysis revealed that there were two miR‐130b target sites within the 3′UTR of PTEN mRNA and experimental evidences demonstrated that miR‐130b repressed the expression of PTEN gene by binding directly to the 3′UTR of PTEN mRNA. These data suggest miR‐130b expression as a target to be inhibited to make tumour cells more sensitive to the toxic impact of TNF‐α.

Mir-142-3p Regulates Inflammatory Response by Contributing to Increased TNF-α in Chronic Rhinosinusitis With Nasal Polyposis

“…10 In addition, TNF-a could induce nuclear factor kB (NF-kB), C-fos, and C-Jun expression and regulate the immunoreaction, which is a broad spectrum of pro-inflammatory cytokines. 11 Previous studies suggested that TNF-a was overexpressed in the lung and nasal mucosa, which played an important role in airway inflammatory responses. 12 However, at present, TNF-a roles in Asian patients with CRSwNP have not been illuminated.…”

Influence of icariin on inflammation, apoptosis, invasion, and tumor immunity in cervical cancer by reducing the TLR4/MyD88/NF-κB and Wnt/β-catenin pathways

“…IL-2 has been used for the treatment of many different kinds of cancer, and Lagunas-Cruz et al reported that IL-2 decreases cervical cancer cell proliferation through the transient arrest of the G1 phase [ 31 ]. TNF‑α, a cytokine naturally synthesized by the macrophages that directly leads to the death of cancer cells [ 32 ]. Meanwhile, the inflammatory cytokines, such as IL-6, IL-8, and IL-1β can promote tumor proliferation and the occurrence and development of cervical cancer [ 28 ].…”

CSNK2A1‐mediated phosphorylation of HMGA2 modulates cisplatin resistance in cervical cancer

“…The incidence of cervical cancer has decreased markedly in developed countries over recent decades, although it remains high in developing countries as a result of unhealthy lifestyles [ 24 ]. Drug resistance is one of the main causes of treatment failure with respect to cervical cancer and various studies have focused on this [ 25 , 26 , 27 ]. In the present study, we found that the phosphorylation level of HMGA2 was associated with the increased chemoresistance in cervical cancer cells.…”