Elevated microRNA‐130b‐5p or silenced ELK1 inhibits self‐renewal ability, proliferation, migration, and invasion abilities, and promotes apoptosis of cervical cancer stem cells

Abstract

Cervical cancer (CC) is the most familiar gynecological malignancy. With the poor prognosis of CC patients, this study explored the effect of microRNA (miR)‐130b‐5p targeting ELK1 expression on self‐renewal ability and stemness of CC stem cells. The tissues of patients with CC or cervical benign lesions were collected. MiR‐130b‐5p and ELK1 expression was detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. Human CC cell line Hela was cultured and the induced CC stem cells were introduced with miR‐130b‐5p mimic or silenced ELK1 to figure their roles in self‐renewal ability, stemness, colony formation, proliferation, migration, invasion abilities, and apoptosis of CC stem cells. Tumor growth was detected in nude mice in vivo. The targeting relationship between miR‐130b‐5p and ELK1 was analyzed using bioinformatic prediction and dual luciferase reporter gene assay. Decreased miR‐130b‐5p and elevated ELK1 existed in CC tissues of patients. Up‐regulated miR‐130b‐5p decreased ELK1 expression in CC stem cells. Elevated miR‐130b‐5p or silenced ELK1 inhibited self‐renewal ability and stemness, colony formation, proliferation, migration and invasion abilities, promoted apoptosis of CC stem cells, as well as decreased the weight and volume of tumor in nude mice. ELK1 was found to be targeted by miR‐130b‐5p. Overexpression ELK1 effectively reversed the cellular phenotypic changes and tumor formation in vivo caused by up‐regulation of miR‐130b‐5p. We conclude that up‐regulated miR‐130b‐5p or silenced ELK1 inhibits CC stem cell growth.

Noncoding RNA actions through IGFs and IGF binding proteins in cancer

“…These actions of miR-130b, although not revealed in cancer models, may shed light on miR-130b actions in cancer. For example, in cervical cancer increased miR-130b-5p was shown to downregulate the transcription factor ELK1 which resulted in decreased stemness, proliferation and migration of cervical cancer cells [82]. Since ELK1 is downstream of IGF1R activation through ERK/ MAPK, IGF-1 is likely to have an intermediary role in this mechanism.…”

Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors

“…The same regulatory effect was also observed in cervical cancer, where the increase in miR-130b-5p (miR-130b-5p is a passenger strand of miR-130b) in cervical cancer stem cells downregulated ETS-like gene 1 (ELK1) expression. Enhancing miR-130b-5p or silencing ELK1 inhibited the self-renewal ability and tumor volume growth of cervical cancer stem cells, and promoted cell apoptosis (Huang & Luo 2021 ). However, opposite views exist.…”

Elk1 enhances inflammatory cell infiltration and exacerbates acute lung injury/acute respiratory distress syndrome by suppressing Fcgr2b transcription

“…Elk1, a member of both the ternary complex factor subfamily and the ETS family, plays essential roles in the regulation of cellular survival, differentiation, growth, and various other biological processes (Yu et al 2021 ). The most popular studies of Elk1 are exploring its roles in cancers, like glioma, bladder, colorectal, and cervical cancers (Wang et al 2020 ; Ma et al 2021 ; Shen et al 2020 ; Huang and Luo 2021 ). Leikauf et al identified Elk1 and other candidate genes related to enhanced susceptibility to ALI in mice using a genetic/genomic approach (Leikauf et al 2011 ) .Significantly, the upregulation of G-protein-coupled receptor 43 has been shown to diminish the inflammatory response and apoptosis, thereby mitigating ALI in lipopolysaccharide (LPS)-induced mice through the modulation of the c-Jun N-terminal kinase/Elk1 pathway (Xu et al 2022 ), indicating that Elk1 performs a role in ALI/ARDS.…”