Reactive oxygen species (ROS) play a pivotal role in biological processes and continuous ROS production in normal cells is controlled by the appropriate regulation between the silver lining of low and high ROS concentration mediated effects. Interestingly, ROS also dynamically influences the tumor microenvironment and is known to initiate cancer angiogenesis, metastasis, and survival at different concentrations. At moderate concentration, ROS activates the cancer cell survival signaling cascade involving mitogen-activated protein kinase/extracellular signal-regulated protein kinases 1/2 (MAPK/ERK1/2), p38, c-Jun N-terminal kinase (JNK), and phosphoinositide-3-kinase/ protein kinase B (PI3K/Akt), which in turn activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF). At high concentrations, ROS can cause cancer cell apoptosis. Hence, it critically depends upon the ROS levels, to either augment tumorigenesis or lead to apoptosis. The major issue is targeting the dual actions of ROS effectively with respect to the concentration bias, which needs to be monitored carefully to impede tumor angiogenesis and metastasis for ROS to serve as potential therapeutic targets exogenously/endogenously. Overall, additional research is required to comprehend the potential of ROS as an effective anti-tumor modality and therapeutic target for treating malignancies.

Tocotrienols, found in several natural sources such as rice bran, annatto seeds, and palm oil have been reported to exert various beneficial health promoting properties especially against chronic diseases, including cancer. The incidence of cancer is rapidly increasing around the world not only because of continual aging and growth in global population, but also due to the adaptation of Western lifestyle behaviours, including intake of high fat diets and low physical activity. Tocotrienols can suppress the growth of different malignancies, including those of breast, lung, ovary, prostate, liver, brain, colon, myeloma, and pancreas. These findings, together with the reported safety profile of tocotrienols in healthy human volunteers, encourage further studies on the potential application of these compounds in cancer prevention and treatment. In the current article, detailed information about the potential molecular mechanisms of actions of tocotrienols in different cancer models has been presented and the possible effects of these vitamin E analogues on various important cancer hallmarks, i.e., cellular proliferation, apoptosis, angiogenesis, metastasis, and inflammation have been briefly analyzed.

Despite the availability of various diagnostic procedures, a tissue biopsy is still indispensable for the routine diagnosis of lung cancer. However, inaccurate diagnoses can occur, leading to inefficient cancer management. In this context, use of circulating microRNAs (miRNAs) may serve as diagnostic tools as liquid biopsies, and as biomarkers to better understand the molecular mechanisms involved in the progression of cancer. We identified miR‐590‐5p as a potential prognostic marker in the progression of non‐small cell lung cancer (NSCLC). We were able to detect this miRNA in blood plasma samples of NSCLC patients through quantitative real‐time PCR. Our data showed an ~7.5‐fold downregulation of miR‐590‐5p in NSCLC patients compared to healthy controls, which correlated with several clinicopathological features. Further, overexpression of miR‐590‐5p led to decreased cell viability, proliferation, colony formation, migration, and invasion potential of lung cancer cells, whereas its knockdown showed the opposite effect. In addition, the levels of several proteins involved in the epithelial‐to‐mesenchymal transition negatively correlated with miR‐590‐5p levels in lung adenocarcinoma cells and tumors of NSCLC patients. Further, dual‐luciferase reporter assays identified STAT3 as a direct target of miR‐590‐5p, which negatively regulated STAT3 activation and its downstream signaling molecules (eg, Cyclin D1, c‐Myc, Vimentin, and β‐catenin) involved in tumorigenesis. Taken together, our study suggests that miR‐590‐5p functions as a tumor suppressor in NSCLC through regulating the STAT3 pathway, and may serve as a useful biomarker for the diagnosis/prognosis of NSCLC, and as a potential therapeutic target for the treatment of NSCLC.

The regulatory roles of long non-coding RNAs in the development of chemoresistance in breast cancer The regulatory roles of long non-coding RNAs in the development of chemoresistance in breast cancer

Dysregulated expression profiles of microRNAs (miRNAs) have been observed in several types of cancer, including non-small cell lung cancer (NSCLC); however, the diagnostic and prognostic potential of circulating miRNAs in NSCLC remains largely undefined. Here we found that circulating miR-320a was significantly down-regulated (~5.87-fold;p< 0.0001) in NSCLC patients (n= 80) compared to matched control plasma samples from healthy subjects (n= 80). Kaplan-Meier survival analysis revealed that NSCLC patients with lower levels of circulating miR-320a had overall poorer prognosis and survival rates compared to patients with higher levels (p< 0.0001). Moreover, the diagnostic and prognostic potential of miR-320a correlated with clinicopathological characteristics such as tumor size, tumor node metastasis (TNM) stage, and lymph node metastasis. Functionally, depletion of miR-320a in human A549 lung adenocarcinoma cells induced their metastatic potential and reduced apoptosis, which was reversed by exogenous re-expression of miR-320a mimics, indicating that miR-320a has a tumor-suppressive role in NSCLC. These results were further supported by high levels of epithelial-mesenchymal transition (EMT) marker proteins (e.g., Beta-catenin, MMP9, and E-cadherin) in lung cancer cells and tissuesviaimmunoblot and immunohistochemistry experiments. Moreover, through bioinformatics and dual-luciferase reporter assays, we demonstrated thatAKT3was a direct target of miR-320a. In addition, AKT3-associated PI3K/AKT/mTOR protein-signaling pathways were elevated with down-regulated miR-320a levels in NSCLC. These composite data indicate that circulating miR-320a may function as a tumor-suppressor miRNA with potential as a prognostic marker for NSCLC patients.