m6A/HOXA10-AS/ITGA6 axis aggravates oxidative resistance and malignant progression of laryngeal squamous cell carcinoma through regulating Notch and Keap1/Nrf2 pathways.

As the second most prevalent malignant tumor of head and neck, laryngeal squamous cell carcinoma (LSCC) imposes a substantial health burden on patients worldwide. Within recent years, resistance to oxidative stress and N6-methyladenosine (m6A) of RNA have been proved to be significantly involved in tumorigenesis. In current study, we investigated the oncogenic role of m6A modified long non coding RNAs (lncRNAs), specifically HOXA10-AS, and its downstream signaling pathway in the regulation of oxidative resistance in LSCC. Bioinformatics analysis revealed that heightened expression of HOXA10-AS was associated with the poor prognosis in LSCC patients, and N (6)-Methyladenosine (m6A) methyltransferase-like 3 (METTL3) was identified as a factor in promoting m6A modification of HOXA10-AS and further intensify its RNA stability. Mechanistically, HOXA10-AS was found to play as a competitive endogenous RNA (ceRNA) by sequestering miR-29 b-3p and preventing its downregulation of Integrin subunit alpha 6 (ITGA6), ultimately enhancing the oxidative resistance of tumor cells and promoting the malignant progression of LSCC. Furthermore, our research elucidated the mechanism by which ITGA6 accelerates Keap1 proteasomal degradation via enhancing TRIM25 expression, leading to increased Nrf2 stability and exacerbating its aberrant activation. Additionally, we demonstrated that ITGA6 enhances γ-secretase-mediated Notch signaling activation, ultimately promoting RBPJ-induced TRIM25 transcription. The current study provides the evidence supporting the effect of m6A modified HOXA10-AS and its downstream miR-29 b-3p/ITGA6 axis on regulating oxidative resistance and malignant progression in LSCC through the Notch and Keap1/Nrf2 pathways, and proposed that targeting this axis holds promise as a potential therapeutic approach for treating LSCC.

A prospective study of the association between serum klotho and mortality among adults with rheumatoid arthritis in the USA.

BACKGROUND: While it is known that klotho has negative regulatory effects in a variety of diseases such as metabolic disorders and kidney disease, the specific role of klotho in rheumatoid arthritis (RA) and its effect on mortality are unclear. This study investigated the association between serum klotho levels and mortality in patients with RA. METHODS: This study included 841 adults with RA from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016 to extract the concentrations of serum klotho. The association between klotho and RA was determined using Cox regression, Kaplan-Meier (KM) curves, and restricted cubic spline (RCS) models. RESULTS: A total of 841 patients with RA were included in this study, who were divided into four groups based on the quartiles of serum klotho levels (Q1, Q2, Q3, and Q4). Cox regression analysis with adjustment for covariates revealed that high levels of klotho lowered the risk of both all-cause and cardiovascular mortality compared to the Q1 group. The KM curve analysis suggested that this effect was more pronounced for all-cause mortality. The RCS-fitted Cox regression model indicated a U-shaped correlation between serum klotho levels and RA mortality. The risk of all-cause mortality increased with decreasing serum klotho levels below a threshold of 838.81 pg/mL. Subgroup analysis revealed that the protective effect of klotho was more pronounced in patients with the following characteristics: male, white ethnicity, age ≥ 60 years, body mass index < 25 kg/m2, estimated glomerular filtration rate ≥ 60 mL/ (min × 1.73 m2), and 25-hydroxyvitamin D level ≥ 50 nmol/L. CONCLUSION: Serum klotho levels had a U-shaped correlation with all-cause mortality in patients with RA, indicating that maintain a certain level of serum klotho could prevent premature death.

[Corrigendum] NORAD regulates epithelial­mesenchymal transition of non­small cell lung cancer cells via miR­422a.

Following the publication of this paper, the authors have realized that they overlooked indicating that Zhikun Chen and Qin Che contributed equally to this work. Therefore, the affiliations for this paper should have been written as follows:  Zhikun Chen1*, Qin Che2* and Chunxue Xie3. Departments of 1Emergency, 2Infectious Diseases and 3General Practice, Jingmen No. 1 People's Hospital, Jingmen, Hubei 448000, P.R. China. *Contributed equally. The authors confirm that there are no further errors in the study, and all the authors agree to this correction. The authors regret their oversight, and apologize for any inconvenience caused. [the original article was published in Molecular Medicine Reports 23: Article no. 111, 2021; DOI: 10.3892/mmr.2020.11750].

NORAD regulates epithelial­mesenchymal transition of non­small cell lung cancer cells via miR­422a.

The poor prognosis of non­small cell lung cancer (NSCLC) is related to epithelial­mesenchymal transition (EMT). Recent studies demonstrated that non­coding RNA activated by DNA damage (NORAD) displays a carcinogenic effect and targets microRNA (miR)­422a, which may be involved in tumor cell migration and invasion. The aim of the present study was to investigate the effect of NORAD on NSCLC cell EMT and the underlying mechanism. Reverse transcription­quantitative PCR and western blotting were performed to detect the expression levels of long non­coding RNAs, miRNAs and mRNAs. Cell viability, migration and invasion were detected by conducting Cell Counting Kit­8, wound healing and Transwell assays, respectively. The target of NORAD was predicted using starBase and further confirmed by conducting a dual­luciferase reporter assay. The results indicated that NORAD expression was significantly increased in lung cancer tissues and cells compared with adjacent healthy tissues and cells. Compared with the control groups, NORAD overexpression promoted SK­MES­1 cell viability, migration and invasion, whereas NORAD knockdown resulted in the opposite effects in A549 cells. Moreover, miR­422a, which was predicted to be a target of NORAD, displayed lower expression levels in lung cancer tissues compared with adjacent healthy tissues. In addition, miR­422a overexpression partially reversed NORAD overexpression­induced increases in SK­MES­1 cell viability, migration, invasion and EMT. In addition, miR­422a knockdown partially reversed the effects of NORAD knockdown. The present study suggested that NORAD regulated lung cancer cell EMT by regulating the expression of miR­422a, providing a potential therapeutic target for the intervention of the development of NSCLC.

Refractory hypertension with massive proteinuria may be reversed in renal artery stenosis patients with low proteinuria selectivity index after stenting.

BACKGROUND: No available prognostic factor was identified for atherosclerotic renovascular stenosis (ARAS) patient who undergo the percutaneous revascularization therapy. REPORT: This is a case of 68-year-old ARAS patient associated with hypertension and massive proteinuria, who exhibited progressive aggravation of renal dysfunction. His proteinuria selectivity index (SI) was only 0.08. Then the stenosis was treated by percutaneous transluminal angioplasty of the renal artery (PTRA) and stenting. After 2-year follow up, all symptoms including renal dysfunction and uncontrolled hypertension was well-controlled. DISCUSSION: As no reliable predictors of clinical response have been identified yet, SI might be a simple prognositic index for ARAS patients undergone the revascularzation therapy.