MicroRNA-181a-5p Impedes IL-17-Induced Nonsmall Cell Lung Cancer Proliferation and Migration through Targeting VCAM-1

Abstract

Aim: The contribution of the inflammatory mediator interleukin-17 (IL-17) in nonsmall cell lung cancer (NSCLC) malignancy has been reported in the literature. MicroRNA-181a-5p (miR-181a-5p) acts as a tumor suppressor which can regulate target gene at the posttranscriptional level. Our study aimed to investigate the interaction between IL-17 and miR-181a-5p in NSCLC. Methods: 35 patients with NSCLC and 24 COPD controls were selected and examined in our study. In vitro, H226 and H460 cell lines were exposed to different doses (20, 40, 60, and 80 ng/mL) of IL-17 to examine the effect of IL-17 on miR-181a-5p and vascular cell adhesion molecule 1 (VCAM-1) expression. MiR-181 mimic and miR-181a-5p inhibitor were transfected to explore the regulation of VCAM-1 as well as tumor cell proliferation and migration. Results: miR-181a-5p expression was downregulated, and IL-17 and VCAM-1 expression was upregulated in NSCLC tissues. Furthermore, IL-17 decreased miR-181a-5p expression but increased VCAM-1 expression in H226 and H460 cells. MiR-181 regulated VCAM-1 expression through binding to 3’-UTR sequence. MiR-181 attenuated tumor cell proliferation and migration. IL-17 modulated miR-181a-5p expression through activating NF-κB but not Stat3. Conclusion: Taken together, our data show the regulation of VCAM-1 expression by miR-181a-5p under IL-17 exposure, predicting a potential way for counteracting cancer metastasis.

Allicin Inhibits Proliferation and Invasion in Vitro and in Vivo via SHP-1-Mediated STAT3 Signaling in Cholangiocarcinoma

“…In our study, we focused on how allicin inhibits CCA cell proliferation and invasion through STAT3 signaling. STAT3 is a key transcription factor involved in inflammation [44], angiogenesis [45], migration, and proliferation [46]. It is considered as an oncogene due to its tumor-promoting effect.…”

Potentially Functional Variants of ATG16L2 Predict Radiation Pneumonitis and Outcomes in Patients with Non–Small Cell Lung Cancer after Definitive Radiotherapy

“…The functional rs1058600 T variant is located in the 3’UTR of the ATG12 primary transcript and in the predicted miRNA-binding site ( miR-181 and miR-494 ) (http://snpinfo.niehs.nih.gov/snpfunc.htm). It has been reported that the miRNA-181 functions as a tumor suppressor or a tumor promotor by influencing expression of the target genes at the posttranscriptional level, 47 and miR-494 expression was correlated with lung cancer progression in mice. 48 These may partly explain the underlying biological and molecular mechanisms for the observed associations, which need to be further investigated.…”

The Pervasive Role of the miR-181 Family in Development, Neurodegeneration, and Cancer

“…In a recent study, the involvement of miR-181a-5p in NSCLC progression has been elucidated by providing also evidence that this miRNA inhibits NSCLC cell proliferation and migration by targeting VCAM-1. The authors also showed that the interplay between miR-181a and VCAM-1 is regulated by the pro-inflammatory cytokine Interleukin (IL)-17 and the NF-κB pathway [47].…”