Chemoresistance remains a great obstacle in effective lung adenocarcinoma (LUAD) treatment. Previously, we verified the role of microRNA-200b (miR-200b) in the formation of docetaxel (DTX)-resistant LUAD cells. This study aims to investigate the mechanism underlying the low level of miR-200b in DTX-resistant LUAD cells. The real-time reverse transcription (RT²) lncRNA PCR array system was applied to explore lncRNAs that potentially regulated miR-200b in DTX-resistant LUAD cells. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) contributed to the low miR-200b level in DTX-resistant LUAD cells. Functional assays were conducted to determine the role of MALAT1 in regulating the growth and metastasis of parental and DTX-resistant LUAD cells. Investigation revealed the mechanism of the competing endogenous RNA (ceRNA) pathway. MALAT1 regulated miR-200b by acting as a ceRNA. MALAT1 modulated the sensitivity of LUAD cells to DTX. E2F transcription factor 3 (E2F3) and zinc-finger E-box binding homeobox 1 (ZEB1) were two targets of miR-200b and mediated the function of MALAT1 in DTX-resistant LUAD cells. Transcription factor AP-2 gamma (TFAP2C) and ZEB1 activated the MALAT1 transcription. In conclusion, TFAP2C-activated MALAT1 modulated the chemoresistance of LUAD cells by sponging miR-200b to upregulate E2F3 and ZEB1. Our findings may provide novel therapeutic targets and perspectives for LUAD treatment.

Circular RNA (circRNA), as a covalently closed circular RNA molecule, is widely present, which is recognized as a competing endogenous RNA. A large number of differentially expressed circRNAs have been identified and are recognized as potential biomarkers for the diagnosis of tumors. CircRNAs play an important role in the regulation of cell signaling pathways. The main biological functions of circRNAs include acting as miRNA sponges, regulating the transcription of the parental genes, and acting as adapters to regulate the interactions between proteins and encoding proteins. Compared with normal tissues, there are differentially expressed circRNAs in lung cancer tissue, and the expression levels of circRNAs are correlated with clinicopathological features of lung cancer. Their roles in pathway regulation are described, and the diagnostic and prognostic values are further evaluated. In lung cancer, circRNAs participate in the proliferation, migration, and invasion, acting as a competitive endogenous RNA. Differentially expressed circRNAs may serve as non-invasive diagnostic markers for lung cancers. Further investigation of the roles of circRNAs in the pathogenesis and regulatory pathways is conducive to the development of novel approaches for the diagnosis and accurate treatment of lung cancers.

Background Nearly 85 % of lung-cancer-specific epidermal growth factor receptor (EGFR) sensitive mutations comprise a substitution at position 858 (21L858R) and deletion mutants in exon 19 (19del). The aim of this study was to assess the role of EGFR mutation subtypes in predicting the efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs) and the prognosis of patients with advanced non-small cell lung cancer (NSCLC). Method We systematically searched for eligible articles investigating the association between EGFR mutation subtypes and the efficacy of EGFR TKIs and the prognosis of patients with NSCLC. The summary risk ratio (RR) and mean difference (MD) were calculated using meta-analysis. In addition, we used variance analysis for the progression-free survival data (PFS) and used the rank sum test for the overall survival data. Results We identified 22 eligible trials involving 1,082 patients. The objective response rate of the 19del mutation group was significantly higher than the 21L858R mutation group (RR 1.23; 95 % CI 1.12–1.36; P < 0.0001). The PFS (MD 3.55; 95 % CI 0.90–6.20; P = 0.009; MD 2.57; 95 % CI 0.51–4.62; P = 0.01) and overall survival (OS) (MD 10.52; 95 % CI 5.10–15.93; P = 0.0001) of the 19del mutation group were significantly longer than the 21L858R mutation group; the same results were observed in the variance analysis and rank sum test. Conclusion The 19del mutation may be a more efficient clinical marker for predicting the response of patients with NSCLC to EGFR TKIs. Furthermore, patients with the 19del mutation have both a longer PFS and OS. The 19del mutation is also the prognostic factor for patients with NSCLC.

Lung squamous cell carcinoma is the second-largest histological subtype of lung cancer, which is the leading cause of cancer-related death worldwide. Lobaplatin, one of the third-generation platinum compounds, has shown encouraging anticancer activity in a variety of tumors. The aim of this study was to determine the therapeutic efficacy of lobaplatin on p53-mutant lung squamous cancer cells SK-MES-1. In order to evaluate the antitumor effect of lobaplatin, several in vitro and in vivo analyses were carried out, including Cell Counting Kit-8 (CCK-8), fluorescence-activated cell sorter, Western blot, and terminal deoxynucleotidyl transferase dUTP nick end labeling. Findings showed that lobaplatin could inhibit cell proliferation and induce apoptosis of SK-MES-1 cells in vitro through both intrinsic and extrinsic apoptotic pathways in a time- and dose-dependent manner. In addition, lobaplatin could arrest cell cycle at S phase in SK-MES-1. Lobaplatin has obvious antitumor efficacy in human SK-MES-1 xenograft models; therefore, it seems to be a promising candidate in lung squamous cancer therapy.

Gambogenic acid (GNA), which is an important active compound present in gamboge, exerts anticancer activity in various types of tumor cells. However, the effect of GNA on small‑cell lung cancer (SCLC) cell lines and the underlying mechanism involved still remain unclear. In the present study, GNA inhibited the proliferation and cell cycle progression of SCLC cells. GNA also promoted the apoptosis of SCLC cells in a dose‑dependent manner, which is associated with modulating the levels of proteins involved in apoptosis pathways in NCI‑H446 and NCI‑H1688 cells. The results demonstrated that GNA increased the level of cleaved caspase‑3, ‑8 and ‑9, and Bax but decreased the expression of anti‑apoptotic protein, Bcl‑2. Furthermore, similar results were obtained in a mouse tumor xenograft model. Additionally, GNA exhibit low toxicity in tissues when administered to mice in the SCLC xenograft models. Collectively, our findings demonstrated that GNA significantly inhibited the proliferation of SCLC cells and promoted cell apoptosis via cell cycle arrest and induction of apoptosis.

Platinum-based chemotherapy is recommended as the first-line treatment regimen for patients with advanced non-small-cell lung cancer (NSCLC). Lobaplatin (LBP), a third-generation platinum anti-neoplastic agent, has shown an improved efficacy. This study is aimed to investigate the mechanisms of LBP-induced apoptosis in the A549 p53 wild-type cell line. The Cell Counting Kit-8 assay (CCK-8), flow cytometry (FCM), Western blot, xenograft tumor models, terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), and RNA interference were used in this study. Our results showed that the proliferation of A549 cells could be inhibited by LBP. At lower concentrations, LBP triggered cell cycle arrest at the G1 phase in A549 cells. LBP could also induce apoptosis of A549 cells. LBP also increased the expression of PARP and Bax and the cleavage of caspase-3, caspase-8, and caspase-9 and reduced Bcl-2 expression. In vivo experiment confirmed that LBP could inhibit tumor growth in the A549 xenograft models and induce apoptosis. Apoptosis of A549 cells was decreased after transfected with p53 shRNA or treated with reactive oxygen species inhibitor NAC and p38MAPK inhibitor SB203580, suggesting that the p53/ROS/p38MAPK pathway appeared to mediate the LBP-induced apoptosis of A549 cells. Our data demonstrate that LBP could be a promising candidate for the treatment of NSCLC with wild-type p53.