A three serum miRNA panel as diagnostic biomarkers of radiotherapy‑related metastasis in non‑small cell lung cancer

Abstract

Serum microRNAs (miRNAs) have been implicated as noninvasive biomarkers for lung cancer diagnosis. However, there are no sensitive and specific biomarkers for the detection of radiotherapy-related non-small cell lung cancer (NSCLC) metastasis. The present study aimed to investigate the role of three serum miRNAs, namely miRNA (miR)-130a, miR-25 and miR-191 * , in diagnosing NSCLC, and their biological functions in radiation-mediated development of metastatic properties in A549 cells. To determine this, serum samples were collected from 84 patients with NSCLC and 42 age-and sex-matched healthy controls. Differential expression of serum miRNAs was analyzed by quantitative PCR. Significant associations between miRNA expression and overall survival of patients with NSCLC were identified using the Cox proportional regression model. A receiver operating characteristic curve was generated to evaluate diagnostic accuracy. The functions of miR-130a, miR-25 and miR-191 * in lung cancer cells were studied by transfecting A549 cells with miRNA mimics and inhibitors. The results of the present study demonstrated that the expression levels of miR-130a, miR-25 and miR-191 * in the serum of patients with NSCLC were increased compared with those in healthy controls, and these increases were associated with advanced age (≥60 years), radiotherapy, histological type (squamous carcinoma), low survival rate and low median survival time. Additionally, irradiation induced the upregulation of miR-130a, miR-25 and miR-191 * expression in A549 cells in vitro and in a xenograft mouse model. Irradiation also promoted the invasiveness of A549 cells in vitro and metastasis in vivo. In conclusion, miR-130a, miR-25 and miR-191 * may be potential biomarkers for the diagnosis of patients with NSCLC and may serve oncogenic roles in radiation-mediated metastasis of NSCLC.

AXL Inhibits Proinflammatory Factors to Relieve Rheumatoid Arthritis Pain by Regulating the TLR4/NF-κB Signaling Pathway

“…TLR4 is a critical member of the TLRs family and one of the upstream molecules of NF- κ B signaling. The expression intensity of NF- κ B and p65 evaluates the activation of NF- κ B (p65 is the transcriptional activation subunit of NF- κ B) [ 39 , 40 ]. In this study, we evaluated the role of TLR4/NF- κ B in AXL in relieving RA pain.…”

Identification of miR-151a as a novel endogenous control for small extracellular vesicle cargo normalization in human cancer

“…One mechanism by which radiotherapy affects the DDR is by altering the expression of translational regulators including miRNAs, which have complex regulatory roles in response to radiation damage, stemming from their involvement in the DNA damage response (47)(48)(49)(50). These changes in the expression of certain miRNAs caused by radiotherapy treatment have also been described in the sEV content in different tumor types such as brain tumors, NSCLC, or cervical cancer (51)(52)(53). We therefore considered radiotherapy as an ideal additional extreme scenario for the validation of our miRNA candidates.…”

The role and mechanism of microRNAs in infections with Streptococcus pneumoniae

“…Compared to the healthy group,the results showed that non-small cell lung cancer (NSCLC) patients had higher serum miR130a, miR25 and miR191 expression levels , and these results were associated with the prognosis and sensitivity to radiation therapy of patients. Meanwhile, the tumorigenic effects of miR130a, miR25 and miR191 were all confirmed in radiation-mediated metastasis of transplanted tumors in mice based on in vitro and in vivo studies, indicating the clinical importance of these three MiRNAs in radiation-mediated lung cancer metastasis [22]. In addition, it was reported that intratumoral injection of miR-29b mimics could greatly restrain prostate cancer development in nude mice, and prostate cancer cells propagation can be reduced by overexpression of miR-29b in a time-dependent manner, which can cause cell death.…”