In previous studies, miR-29s showed tumor suppressor properties against lung cancer, which improved the survival of patients upon the administration of chemotherapy via an unknown mechanism. Here, we investigated the regulatory effects of miR-29s on the cisplatin resistance of NSCLC cells. The expression of miR-29s was assessed in 130 clinical patients and in cisplatin-treated NSCLS cell lines. MiR-29c expression was decreased in 77% of NSCLC patients. Cisplatin treatment increased the expression of miR-29c and decreased the expression of its oncogenic target AKT2 in NSCLC cell lines. A Kaplan–Meier survival analysis indicated that higher miR-29c levels led to a longer disease-free survival. In particular, patients who experienced cancer recurrences after cisplatin chemotherapy exhibited a lower level of miR-29c expression, suggesting that miR-29c activation may contribute to the chemotherapeutic efficiency of cisplatin. The enforced expression of miR-29c enhanced the cisplatin sensitivity of NSCLC cells, while the knocking down of miR-29c led to cisplatin resistance. MiR-29c amplified the therapeutic effects of cisplatin in vivo. Rescue experiments suggested that miR-29c regulates the cisplatin resistance of NSCLS cells by negatively regulating the PI3K/Akt pathway. Overall, our results demonstrated that miR-29c enhances the sensitivity of NSCLC cells to cisplatin by targeting the PI3K/Akt pathway.

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GINS complex subunit 2 (GINS2) controls DNA replication. GINS2 expression is upregulated in several kinds of aggressive tumors. However, the effect of GINS2 in lung cancer remains unclear. We performed TCGA database analysis to confirm the clinical significance of GINS2 in lung cancer. After silencing GINS2 in A549 cells, we performed MTT assays, flow cytometry assays, colony formation assays, cell cycle analyses and RNA sequence analysis to elucidate the effect of GINS2 on lung cancer. Moreover, we assessed tumor growth and analyzed body fluorescence in mice as a measure of tumor burden. The TCGA database analysis demonstrated that GINS2 mRNA and protein was highly expressed in three kinds of lung cancer tissues. Subsequently, knockdown of GINS2 inhibited cell proliferation, colony formation, cell cycle arrest and apoptosis in A549 cells. On the other hand, we also investigated the effect of GINS2 on tumor formation in vivo. The analysis of nude mouse tumors showed that the tumor volume and weight of shGINS2 mice were significantly smaller than those of the control mice. To reveal the mechanism of GINS2 in lung cancer, we collected A549 cells with GINS2 knockdown to examine the downstream gene expression changes. The results showed that STAT1 and STAT2 mRNA and protein expression were significantly upregulated after GINS2 knockdown in A549 cells. Our results suggest that GINS2 inhibits the proliferation of lung cancer cells by inhibiting the STAT signaling pathway, which may be a potential biomarker for the diagnosis or prognosis of lung cancer.

Purpose: To investigate the efficacy and safety of selective radiotherapy after distant metastasis of nasopharyngeal carcinoma (NPC) treated with dose-dense cisplatin plus fluorouracil. Materials and Methods: Eligible patients were randomly assigned to a study group treated with dose-dense cisplatin plus fluorouracil following selective radiotherapy and a control group receiving traditional cisplatin plus fluorouracil following selective radiotherapy according to a 1:1 distribution using a digital random table method. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, relapse or progression rate in the radiation field and treatment toxicity. Results: Of 52 patients in the study group, 20 cases underwent radiotherapy., while in the control group of 51 patients, 16 underwent radiotherapy. The median PFS, median OS, survival rates in 1, 2 and 3 years in study and control group were 20.9 vs 12.7months, 28.3 vs 18.8months, 85.2%vs 65.9%, 62.2% vs 18.3%, and 36.6%vs 5.2% (p values of 0.00, 0.00, 0.04, 0.00 and 0.00, respectively). Subgroup analysis showed that the median OS and survival rates of 1, 2, 3 years for patients undergoing radiotherapy in the study group better than that in control group( 43.2vs24.1 months, 94.1% vs 86.7%, 82.4% vs 43.3%, 64.7% vs 17.3%, (p=0.00, 0.57, 0.04 and 0.01, respectively). The complete response rate, objective response rate after chemotherapy and three months after radiotherapy, relapse or progression rate in radiation field in study group and in control group were 19.2% vs 3.9%, 86.5% vs 56.9%, 85% vs 50%, 95% vs 81.3% and 41.3% vs 66.7% (p =0.03, 0.00, 0.03,0.30, 0.01 respectively). The grade 3-4 acute adverse reactions in the study group were significantly higher than in the control group (53.8% vs 9.8%, p=0.00). Conclusions: The survival of patients benefits from selective radiotherapy after distant metastasis of NPC treated with dose-dense cisplatin plus fluorouracil.