Deep understanding of the genomic and immunological differences between Chinese and Western lung cancer patients is of great importance for target therapy selection and development for Chinese patients. Here we report an extensive molecular and immune profiling study of 245 Chinese patients with non-small cell lung cancer. Tumor-infiltrating lymphocyte estimated using immune cell signatures is found to be significantly higher in adenocarcinoma (ADC, 72.5%) compared with squamous cell carcinoma (SQCC, 54.4%). The correlation of genomic alterations with immune signatures reveals that low immune infiltration was associated with EGFR mutations in ADC samples, PI3K and/or WNT pathway activation in SQCC. While KRAS mutations are found to be significantly associated with T cell infiltration in ADC samples. The SQCC patients with high antigen presentation machinery and cytotoxic T cell signature scores are found to have a prolonged overall survival time.

No abstract

miR-154 has been proven to act as a tumor suppressor in several types of tumors. However, its role in non-small cell lung cancer (NSCLC) remains unclear. Thus, the aim of this study was to investigate the effects of miR-154 on NSCLC tumorigenesis and development. Using real-time quantitative PCR (qRT-PCR), we analyzed expression of miR-154 at the transcriptional level in 40 NSCLC tumor tissues and matched adjacent normal tissues and the correlation with clinicopathological features of the patients. The miR-154 mimic was stably transfected into NSCLC A549 cells, and the effects of miR-154 on cancer cell proliferation, colony formation, cell cycle arrest, apoptosis, migration and invasion in vitro, and on the growth of in vivo xenografts were investigated. miR-154 expression levels were significantly downregulated in the NSCLC compared to the corresponding non-cancerous lung tissues (P<0.05), and decreased miR-154 expression was significantly associated with metastasis (P<0.001), larger tumor size (P<0.001) and advanced TNM stage (P<0.001). Furthermore, transfection of the miR-154 mimic into the NSCLC A549 cells was able to inhibit cell proliferation, colony formation, invasion and migration, and induce cell apoptosis and G0/G1 cell cycle arrest. Enforced expression of miR-154 also suppressed the growth of cancer cell xenografts in vivo. These findings indicate that miR-154 may become a potential target for miR-based therapy of NSCLC.

Background: The HOXA cluster antisense RNA 2 (HOXA-AS2) has recently been discovered to be involved in carcinogenesis in multiple cancers. However, the role and underlying mechanism of HOXA-AS2 in non-small cell lung cancer (NSCLC) yet need to be unraveled. Methods: HOXA-AS2 expression in NSCLC tissues and cell lines was detected using quantitative real-time PCR (qRT-PCR). Furthermore, the effects of HOXA-AS2 on NSCLC cell proliferation, apoptosis, migration, and invasion were assessed by MTS, flow cytometry, wound healing and transwell invasion assays, respectively. Starbase2.0 predicted and luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the association of HOXA-AS2 and miR-520a-3p in NSCLC cells. Results: Our results revealed that HOXA-AS2 in NSCLC tissues were up-regulated and cell lines, and were associated with poor prognosis and overall survival. Further functional assays demonstrated that HOXA-AS2 knockdown significantly inhibited NSCLC cell proliferation, induced cell apoptosis and suppressed migration and invasion. Starbase2.0 predicted that HOXA-AS2 sponge miR-520a-3p at 3′-UTR, which was confirmed using luciferase reporter and RIP assays. miR-520a-3p expression was inversely correlated with HOXA-AS2 expression in NSCLC tissues. In addition, miR-520a-3p inhibitor attenuated the inhibitory effect of HOXD-AS2-depletion on cell proliferation, migration and invasion of NSCLC cells. Moreover, HOXA-AS2 could regulate HOXD8 and MAP3K2 expression, two known targets of miR-520a-3p in NSCLC. Conclusion: These findings implied that HOXA-AS2 promoted NSCLC progression by regulating miR-520a-3p, suggesting that HOXA-AS2 could serve as a therapeutic target for NSCLC.

No abstract