Radiotherapy is one of the major cancer treatment strategies. Exposure to penetrating radiation causes cellular stress, directly or indirectly, due to the generation of reactive oxygen species, DNA damage, and subcellular organelle damage and autophagy. These radiation-induced damage responses cooperatively contribute to cancer cell death, but paradoxically, radiotherapy also causes the activation of damage-repair and survival signaling to alleviate radiation-induced cytotoxic effects in a small percentage of cancer cells, and these activations are responsible for tumor radio-resistance. The present study describes the molecular mechanisms responsible for radiation-induced cellular stress response and radioresistance, and the therapeutic approaches used to overcome radioresistance.

The role of tumor microenvironment in therapeutic resistance

Long non-coding RNAs (lncRNAs) are classified as RNAs that are longer than 200 nucleotides and cannot be translated into protein. Several studies have demonstrated that lncRNAs are directly or indirectly involved in a variety of biological processes and in the regulation of gene expression. In addition, lncRNAs have important roles in many diseases including cancer. It has been shown that abnormal expression of lncRNAs is observed in several human solid tumors. Several studies have shown that many lncRNAs can function as oncogenes in cancer development through the induction of cell cycle progression, cell proliferation and invasion, anti-apoptosis, and metastasis. Oncogenic lncRNAs have the potential to become promising biomarkers and might be potent prognostic targets in cancer therapy. However, the biological and molecular mechanisms of lncRNA involvement in tumorigenesis have not yet been fully elucidated. This review summarizes studies on the regulatory and functional roles of oncogenic lncRNAs in the development and progression of various types of cancer.

Non-small cell lung cancer (NSCLC) is one of the leading causes of death in the world. NSCLC diagnosed at an early stage can be highly curable with a positive prognosis, but biomarker limitations make it difficult to diagnose lung cancer at an early stage. To identify biomarkers for lung cancer development, we previously focused on the oncogenic roles of transcription factor TFAP2C in lung cancers and revealed the molecular mechanism of several oncogenes in lung tumorigenesis based on TFAP2C-related microarray analysis. In this study, we analyzed microarray data to identify tumor suppressor genes and nine genes downregulated by TFAP2C were screened. Among the nine genes, we focused on growth arrest and DNA-damage-inducible beta (GADD45B) and phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) as representative TFAP2C-regulated tumor suppressor genes. It was observed that overexpressed TFAP2C resulted in inhibition of GADD45B and PMAIP1 expressions at both the mRNA and protein levels in NSCLC cells. In addition, downregulation of GADD45B and PMAIP1 by TFAP2C promoted cell proliferation and cell motility, which are closely associated with NSCLC tumorigenesis. This study indicates that GADD45B and PMAIP1 could be promising tumor suppressors for NSCLC and might be useful as prognostic markers for use in NSCLC therapy.

Since lung cancer is a major causative for cancer-related deaths, the investigations for discovering biomarkers to diagnose at an early stage and to apply therapeutic strategies have been continuously conducted. Recently, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are being exponentially studied as promising biomarkers of lung cancer. Moreover, supportive evidence provides the competing endogenous RNA (ceRNA) network between lncRNAs and miRNAs participating in lung tumorigenesis. This review introduced the oncogenic or tumor-suppressive roles of lncRNAs and miRNAs in lung cancer cells and summarized the involvement of the lncRNA/miRNA ceRNA networks in carcinogenesis and therapeutic resistance of lung cancer.

DANGER is involved in high glucose-induced radioresistance through inhibiting DAPK-mediated anoikis in non-small cell lung cancer