MicroRNA-21 regulates the proliferation and apoptosis of cervical cancer cells via tumor necrosis factor-α

Abstract

The proliferation and apoptosis of tumor cells are regulated by a variety of microRNAs (miRs). miR-21 can inhibit the apoptosis of cancer cells in vitro. Tumor necrosis factor α (TNF-α) serves an important role in the induction of proliferation of cervical cancer cells. Previous studies have demonstrated that the expression level of miR-21 is associated with TNF-α expression in alveolar macrophages. However, to the best of our knowledge, whether miR-21 regulates TNF-α in cervical cells has not been reported. The present study was designed to investigate whether miR-21 regulates TNF-α expression, proliferation and apoptosis of cervical cancer cells. miR-21, miR-21 inhibitor and control miRNA were synthesized and transfected into HeLa cervical cancer cells. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression levels of miR-21 and TNF-α at the mRNA level. Western blotting was used to measure the expression levels of TNF-α at the protein level. MTT assay and Hoechest-33342 staining were used to measure the proliferation and apoptosis of HeLa cells. miR-21 was identified to upregulate the mRNA and protein expression levels of TNF-α. Furthermore, upregulation of TNF-α enhanced the proliferation capability of HeLa cells. Changes in the expression levels of miR-21 and TNF-α did not significantly affect the apoptosis of Hela cells. In conclusion, the present study demonstrated that miR-21 regulates the expression of TNF-α in HeLa cells. Additionally, the expression level of TNF-α was positively associated with the proliferation capability of Hela cells, but not apoptosis. Therefore, miR-21 regulates the proliferation of HeLa cells through regulation of TNF-α. These results provide novel potential therapeutic targets for the treatment of cervical cancer.

Pathogenic role of exosomes and microRNAs in HPV‐mediated inflammation and cervical cancer: A review

“…miR‐21 may be implicated in the pro‐inflammatory process in cervicitis. Diverse target genes have been identified for miR‐21, including programmed cell death 4 (PDCD4), phosphatase and tensin homolog (PTEN), tissue inhibitor of metalloproteinases‐3 (TIMP‐3), TNF‐α and annexin A1 (ANXA1) . miR‐21 upregulation increased IL‐6 (which is involved in inflammation and tumor development) and α‐SMA (a fibroblast marker) in HeLa‐conditioned media‐treated fibroblasts, while it significantly diminished PDCD4 expression in CC tissues .…”

“…TNF‐α is one of the most important miR‐21 target genes, as a pro‐inflammatory cytokine and a regulator of cell growth. miR‐21 may cause inflammation in CC by upregulating TNF‐α . Interestingly, TNF‐α can play both anticancer and procancer roles and can be negatively regulated by miR‐130a in CC.…”

“…miR-21 may cause inflammation in CC by upregulating TNF-α. 117 Interestingly, TNF-α can play both anticancer and procancer roles and can be negatively regulated by miR-130a in CC. Low levels of TNF-α can stimulate NF-κB expression to upregulate miR-130a expression.…”

The Effects of miR-195-5p/MMP14 on Proliferation and Invasion of Cervical Carcinoma Cells Through TNF Signaling Pathway Based on Bioinformatics Analysis of Microarray Profiling

“…As a member of TNF superfamily of cytokines, TNF mediates cell processes such as inflammation, differentiation, proliferation and apoptosis [12]. More specifically, it has been proved that TNF has certain correlation with CC [1]. A previous study has suggested that MMP14 silencing results in a better treatment of patients resistant to anti-TNF therapy [13].…”

“…Over 50 million new patients are diagnosed with CC yearly around the world, especially in developing countries, which account for over 80% of all worldwide cases [1][2][3]. Conventionally, radiotherapy and chemotherapy individually or both have been used for CC treatment.…”