MicroRNA-25-3p promotes cisplatin resistance in Non-small-cell lung carcinoma (NSCLC) through adjusting PTEN/PI3K/AKT route.

MicroRNAs exert crucial effects in the drug resistance. The purpose of this research was to investigate the miR-25-3p effects on DDP resistance in NSCLC. We used RT-qPCR to evaluate the expression of miR-25-3p. Cell growth was determined using MTS assay. Cellular bio-activity was analyzed via Colony formation, Annexin V/PI, and Transwell assay. Luciferase reporter assay was used to determine miR-25-3p and PTEN binding. Western blot was used to determine PTEN, PI3K, p-AKT/AKT expression. In-vivo study was used to determine the effects of miR-25-3p on the tumor growth. Expression of miR-25-3p is increased in NSCLC cisplatin resistant A549 and H1299 cells. Furthermore, miR-25-3p mimic enhanced drug resistance, and accelerated cell invasion and metastasis. Moreover, miR-25-3p mimic resulted in the activation of PTEN/PI3K/AKT pathway. However, miR-25-3p inhibitors exhibited the opposite trend. We further identified PTEN as a potential target of miR-25-3p. PTEN knockout promoted cisplatin resistance, while PTEN mimic displayed opposite effects. Interestingly, miR-25-3p further boosted cisplatin resistance cells in vivo, and miR-25-3p inhibitors reduced the in-vivo tumor volume. MiR-25-3p/PTEN/PI3K/AKT axis might accelerate DDP tolerance in NSCLC, which may serve as a potential target for chemotherapy resistance in NSCLC.

Pirin is a nuclear redox-sensitive modulator of autophagy-dependent ferroptosis.

In regulated cell death, genetically encoded molecular machinery destroys cells. This process is not only essential for organ development and homeostasis, but also leads to pathological diseases. One form of regulated cell death is ferroptosis, which is an iron-dependent oxidative cell death caused by lipid peroxidation. Although inducing ferroptosis is an emerging anticancer strategy, the molecular mechanism underlying tumor resistance to ferroptotic cell death is still unclear. Here, we show that pirin (PIR), an iron-binding nuclear protein, plays a previously unrecognized role in mediating ferroptosis resistance in human pancreatic cancer cells. The transcription factor NFE2L2 mediates the upregulation of PIR during ferroptosis caused by small-molecule compounds (e.g., erastin or RSL3). PIR is a nuclear redox sensor and regulator, and increasing it limits the oxidative damage of DNA and the subsequent cytoplasmic transport and extracellular release of HMGB1. In contrast, the depletion of PIR initiates HMGB1-dependent autophagy by binding to BECN1, and subsequently promotes ferroptosis by activating ACSL4. Consequently, in cell cultures and xenograft mouse models, blocking PIR signaling enhances ferroptosis-mediated tumor growth suppression. Together, these findings provide new insights into the molecular mechanisms of autophagy-dependent ferroptosis.

Anticancer activity of green synthesised gold nanoparticles from Marsdenia tenacissima inhibits A549 cell proliferation through the apoptotic pathway.

Gold nanoparticles (AuNPs) as the most excellent anticancer theranostic nanoparticles were synthesized through efficient, simple, and green synthesis method using Marsdenia tenacissima plant extracts and they are widely characterized by several techniques including ultraviolet-visible (UV) spectroscopy, atomic force microscopy (AFM), energy-dispersive X-ray spectrometers (EDS), transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy. From the AuNPs synthesized by M. tenacissima extracts, it was discovered that particle size around 50 nm, which is admirable nano dimension, was achieved by plant-mediated synthesis. After characterization of these nanoparticles, they performed as in vitro anticancer activity against lung cancer cell lines (A549). MTT assay revealed that AuNPs produce toxicity based on the dose-dependent A549 cells growth inhibition. AuNPs treatment activates caspase expression and down-regulates the anti-apoptotic protein expression in A549 cells. Our results point out that the AuNPs from M. tenacissima extract are apposite stabilizing agents, which serve as an effective anticancer agent against lung cancer cell lines (A549).

KIF2C exerts an oncogenic role in nonsmall cell lung cancer and is negatively regulated by miR-325-3p.

Nonsmall cell lung cancer (NSCLC) is one of the leading causes of cancer-related death worldwide. Kinesin family member 2C (KIF2C), a modulator in microtubule depolymerization, bipolar spindle formation, and chromosome segregation, has been reported to take roles in cancer biology, but its role in NSCLC remains unclear. This study was intended to investigate the expression and function of KIF2C in NSCLC. Our results demonstrated that KIF2C was up-regulated in NSCLC tissues and cell lines. The high expression of KIF2C in NSCLC tissues was significantly correlated with higher T stage (0.0078), worse differentiation status (0.0049), and lymph node metastasis (P < .0001). We also proved that the high expression level of KIF2C predicted worse prognosis of the patients. After knockdown of KIF2C, the proliferation and metastasis of NSCLC cells were inhibited. Luciferase reporter assay suggested that KIF2C was a target gene of miR-325-3p, which was reported to be a tumour suppressor in NSCLC. In conclusion, this study proved an oncogenic role of KIF2C in NSCLC and partly clarified the mechanism of its high expression. Our findings provided a useful insight into the mechanism of NSCLC progression and offered clues to novel therapy strategies.

lncRNA KIAA0125 functions as a tumor suppressor modulating growth and metastasis of colorectal cancer via Wnt/ß-catenin pathway.

Colorectal cancer (CRC) is the third most common cancer in all races worldwide in recent years. The survival of the CRC patients is mostly affected by the stage of the disease at the time of diagnosis. Thus, the current challenge is to find sensitive and reliable biomarkers in early screening of CRC. Recently, emerging evidence has shown that long non-coding RNAs (lncRNAs) may play crucial roles in tumorigenesis. In this study, we found that lncRNA KIAA0125 was downregulated in colorectal tissues and cells. The functional study demonstrated that overexpression of KIAA0125 suppressed cell proliferation, migration, and invasion whereas the reversal effects were seen in silencing experiment. Besides, KIAA0125 inhibited epithelial-mesenchymal transition through Wnt/ß-catenin signaling in CRC. Our findings suggested that KIAA0125 may act as an oncosupressor gene and could be considered as a potential diagnosis biomarker in CRC.

Aspirin ameliorates lung cancer by targeting the miR-98/WNT1 axis.

BACKGROUND: Aspirin, an anti-inflammatory drug, has been widely investigated in the treatment of many cancer types, including colorectal, ovarian, breast, and prostate cancers. MicroRNAs (miRNAs) are the most well studied noncoding RNAs in cancers. In the current study, we were interested in defining the function of aspirin in lung cancer treatment and the related noncoding RNAs involved in this process. METHODS: The function of aspirin in lung cancer growth was evaluated by cell viability and colony formation assays. Screening of miRNAs affected by aspirin was performed through quantitative real-time PCR. Prediction of miR-98 targeting WNT1 was performed using online bioinformatics software and was further confirmed by luciferase reporter gene analysis. The levels of miR-98 and WNT1 were tested through immunoblotting and quantitative real-time PCR analysis in lung cancer cells under aspirin treatment. RESULTS: Cell viability was sharply suppressed in lung cancer cells with an increasing dose of aspirin. Aspirin markedly weakened the malignant colony formation ability of lung cancer cells. One out of six tumor suppressor miRNAs could be obviously regulated by aspirin in lung cancer cells. The inhibition of miR-98 on the luciferase activities of wild-type 3' untranslated region vectors of WNT1 was clearly revealed in lung cancer cells. Meanwhile, the inhibitor of miR-98 increased the luciferase activities of wild-type 3' untranslated region vectors of WNT1. After treatment with aspirin the expression of miR-98 was induced and then its target gene, WNT1, was depressed in the cells. CONCLUSION: Aspirin targets the miR-98/WNT1 axis to ameliorate lung cancer development.