SAHA, a member of histone deacetylase inhibitors (HDACIs), which emerged as a class of novel antitumor drug, has been used in clinical treatment of cancers. However, clinical experience of SAHA in solid tumors has been disappointing. Nevertheless, the underlying mechanism of this deficiency is not clearly understood. In the present study, we found that SAHA could induce epithelial-mesenchymal transitions (EMT) in lung cancer A549 cells, which was associated with increased migration capability and cellular morphology changes. We showed that SAHA decreased epithelial marker E-cadherin's expression and increased the expression of mesenchymal marker vimentin. SAHA upregulated the protein and mRNA expression of transcription factor Slug in a time-dependent manner and promoted its nuclear translocation. We further demonstrated that SAHA upregulated Slug expression by promoting Slug acetylation but not influencing the phosphorylation of GSK-3β, a main kinase-controlled Slug expression. Finally, silencing of Slug by siRNA reversed EMT marker expressions and cellular morphology change induced by SAHA, suggesting that Slug plays a crucial role in SAHA-mediated EMT in A549 cells. Our research study provided a better understanding of treatment failure of SAHA in patients with solid tumors. Therefore, more attention should be paid to cancer treatment using SAHA and strategies for reversing EMT before using SAHA would be better if the value of SAHA in the treatment of solid tumors, especially lung cancer, is realized.

BackgroundLung cancer has become a leading disease for the tumor-induced mortality. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers. The present research aimed to evaluate the correlation between the anaplastic lymphoma kinase/oncogene or c-ros oncogene 1 (ALK/ROS1) fusions or mutations of epidermal growth factor receptor (EGFR) and ages or gender of patients.Material/MethodsAmong 1449 NSCLC patients, 457 patients who were diagnosed as consecutive EGFR mutations or ALK/ROS1 fusions between November 2016 and February 2018 were involved in the present study. EGFR genes or ALK/ROS1 mutations were detected by using DNA sequencing technique and amplification-refractory mutation system (ARMS). The mRNAs of ROS1 and ALK fusion were examined by using polymerase chain reaction technique and fusion gene detection kit.ResultsFemales were more often inflicted by the EGFR mutations, especially for the exon 19 deletion and L858R mutation. There were significantly more ALK/ROS1 fusions in females compared to males (P<0.05) and significantly more ALK/ROS1 fusions in <60 years of age patients compared to patients older than 60 years of age (P<0.05). Exon 21 L858R and L861Q dominantly occurred in patients ≥60 years of age and exon 19 deletion in patients <60 years of age. EML-ALK-1 mainly existed in the female NSCLC patients.ConclusionsEGFR mutations and ALK/ROS1 fusions mainly occurred in the NSCLC female patients who were older than 60 years of age.

Background Diagnosis of rare diseases remains a challenge in China. We describe our experience with Birt-Hogg-Dubé syndrome (BHDS) encountered at a Rare Lung Disease Clinic recently established in China. Methods After the first patient with BHDS was recognized in 2017, a Rare Lung Disease Clinic with a multidisciplinary team of specialists was established. We retrospectively analyzed the data of consecutive patients with BHDS encountered from inception to December 2021. Results There were 1, 1, 15, 12 and 21 cases with BHDS diagnosed from year 2017 to 2021, respectively. All 50 patients (34 women) were of Han race with a mean age of 47.4 years. The common manifestations were pulmonary cysts (98%), pneumothorax (54%) and skin lesions (68%). Renal cancer was detected in two patients and renal angiomyolipoma in four other patients. The main presentations leading to diagnosis were pneumothorax (42%), family screening (36%), and lung cysts identified on radiologic imaging (20%). The average delay in diagnosis was 8.3 years, and 4.7 years in patients with only pulmonary cysts. The most frequent pathogenic variant was c.1285del/dup on exon 11 (23%) among 44 patients confirmed by genetic testing. Renal cancer has not been found on follow-up surveillance thus far. Conclusions Increasing number of patients with BHDS are being recognized in China, facilitated by establishment of a Rare Lung Disease Clinic. Pulmonary cysts and pneumothorax were commonly encountered features, but skin lesions appeared to be more prevalent in Chinese subjects than previously reported in other Asian countries.

Purpose: As miR-34c acts as a tumor suppressant for multiple cancers, the purpose of this study was to investigate that role that miR-34c plays in the proliferation and apoptosis of lung cancer. Methods: The expression of miR-34c in 600 patients with lung cancer was quantitatively analyzed with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) technology and correlated to clinical pathological parameters. The CCK-8 analysis and flow cytometry were carried out to detect cell proliferation and apoptosis in miR-34c-mimic transfected cell lines. Moreover, the regulation of miR-34c to interleukin-6 (IL-6) in cell lines was detected by western blot, qRT-PCR and dual-luciferase reporter assay. Results: The expression of miR-34c was downregulated in lung cancer compared with adjacent normal tissues. The expression level of miR-34c was linked to stromal invasion. Furthermore, overexpressing miR-34c played an active role in effectively inhibiting cell proliferation and inducing apoptosis. In addition, a significant inverse relationship was exhibited between the expression of miR-34c and IL-6 in tumor tissues. Conclusion: At the molecular level, IL-6 can be used as a direct target of miR-34c in the treatment of lung cancer cells and miR-34c can be used as an effective biomarker and therapeutic target for lung cancer.