MicroRNA‑889‑3p targets FGFR2 to inhibit cervical cancer cell viability and invasion

Abstract

MicroRNAs (miRNAs) are frequently dysregulated in cervical cancer, and the aberrant regulation of miRNAs may be involved in the regulation of various cancer-associated biological processes. Therefore, further exploration of the specific roles of dysregulated miRNAs in cervical cancer and their associated mechanism may promote the development of effective therapeutic approaches. miRNA-889-3p (miR-889) serves crucial roles in esophageal squamous cell carcinoma and hepatocellular carcinoma. However, to the best of our knowledge, no studies concerning the relationship between miR-889 and cervical cancer were performed. The aims of this study were to measure miR-889 expression in cervical cancer and to examine the potential effects of miR-889 in cervical cancer development on a molecular level to provide potential clinical insight. The present study revealed that miR-889 was downregulated in cervical cancer tissues and cell lines. Reduced miR-889 expression was significantly associated with International Federation of Gynecology and Obstetrics cancer staging and with lymph node metastasis. In addition, miR-889 overexpression reduced cervical cancer cell viability and invasive ability. Using bioinformatics analysis, fibroblast growth factor receptor 2 (FGFR2) was predicted to be a potential target of miR-889, which was confirmed using luciferase reporter assay. Reverse transcription-quantitative PCR and western blot analysis results suggested that miR-889 overexpression decreased FGFR2 expression in cervical cancer cells at the mRNA and the protein level, respectively. Conversely, FGFR2 silencing using small interfering RNA imitated the tumor suppressive effects of miR-889 overexpression in cervical cancer cells, which was successfully reversed by plasmid-facilitated FGFR2 overexpression. These observations demonstrated that miR-889 may serve tumor suppressive roles in cervical cancer by directly targeting FGFR2, which indicated that this miRNA may be a promising therapeutic target for patients with cervical cancer.

<p>Long Noncoding RNA <em>ZFPM2-AS1</em> Enhances the Malignancy of Cervical Cancer by Functioning as a Molecular Sponge of microRNA-511-3p and Consequently Increasing FGFR2 Expression</p>

“…41,42 Functionally, FGFR2 is believed to serve as an oncogene enhancing the malignant characteristics of cervical cancer. 43 Here, our results confirmed that ZFPM2-AS1 can positively regulate FGFR2 expression by functioning as a ceRNA of miR-511-3p in cervical cancer, thereby pointing to possible diagnostics and therapeutics based on the ZFPM2-AS1-miR-511-3p-FGFR2 axis.…”

“…To decipher the mechanism underlying the involvement of miR-511-3p in cervical cancer progression, we carried out bioinformatics analysis to find a downstream target of miR-511-3p. The 3′-UTR of FGFR2 mRNA was found to contain complementary binding sequences for the seed region of miR-511-3p ( Figure 5A), and FGFR2 was selected for further experimental verification because this gene is involved in the cervical carcinogenesis and cancer progression [41][42][43] in addition to being regulated by multiple miRNAs. [44][45][46] The luciferase reporter assay was performed to verify the above prediction.…”

Mir-3150B-3P Inhibits the Proliferation and Invasion of Cervical Cancer Cells by Targeting Tnfrsf11A

“…14 Sun et al demonstrated that miR-889-3p reduced CC cell growth and invasion via targeting fibroblast growth factor receptor 2. 15 However, the expression and underlying roles of miR-3150b-3p in CC remain elusive. We suggested that miR-3150b-3p may serve as a tumor suppressor in CC.…”

miR‐874‐3p inhibits cell migration through targeting RGS4 in osteosarcoma

“…MicroRNAs (miRNAs) are small short‐strand non‐coding endogenous conserved single‐stranded molecule RNAs with a length of 18–25 nucleotides, which regulate gene expression by inhibiting specific sites in the 3′ untranslated region of its target genes 8,9 . miRNA is widely found in eukaryotes and usually has a length of 18–25 nucleotides, and the 3' end can vary from 2 to 3 nucleotides, with varying lengths 10 .…”