Migration Of Small Cell Lung Cancer Cells Research Articles

Upregulation of lncRNA PINK1-AS Predicts the Distant Metastasis of Patients with Small Cell Lung Cancer.

PINK1-AS has been shown to participate in gastric cancer, while its role in other tumors is unclear. This study was carried out to explore the participation of PINK1-AS in small cell lung cancer (SCLC). In this study, the expression of PINK1-AS in SCLC and paired non-cancer tissues from 60 SCLC patients and in plasma samples from 60 SCLC patients and 60 healthy controls was analyzed with RT-qPCR. Chi-squared t test was applied to analyze the associations between plasma expression levels of PINK1-AS and the clinical factors of the patients. Patients were followed up for 5years to explore the role of PINK1-AS in the prognosis of SCLC. ROC curve analysis was applied to explore the role of PINK1-AS in the prediction of distant metastasis. Transwell assays were performed to evaluate the role of silencing and overexpression of PINK1-AS in the invasion and migration of SCLC cells. We found that PINK1-AS was upregulated in SCLC tissues compared to that in non-cancer tissues. Plasma expression levels of PINK1-AS were increased in SCLC patients compared to that in the controls. High plasma expression levels of PINK1-AS were closely associated with worse survival. Plasma expression of PINK1-AS was only closely correlated with distant tumor metastasis, but not other factors. High plasma expression levels of PINK1-AS effectively separated patients with distant metastasis from non-metastatic patients. Moreover, PINK1-AS positively regulated the migration and invasion of SCLC cells. Therefore, the upregulation of PINK1-AS predicts the distant metastasis of patients with SCLC.

Long Noncoding RNA H19 Facilitates Small Cell Lung Cancer Tumorigenesis Through miR-140-5p/FGF9 Axis.

PurposeLong noncoding RNAs (lncRNAs) are emerging as gene regulators to drive many important cancer phenotypes through interaction with microRNAs. There have been numerous data about upregulation of H19 and its strong oncogenic function in progression of cancers. However, the function and detailed mechanisms of H19 on small cell lung cancer (SCLC) are still unclear.MethodsIn this study, we investigated H19 expression in SCLC and para-carcinoma tissues. We also explored the function and detailed mechanisms of H19 on SCLC cells via RT-PCR, transwell assay, Western blot, dual-luciferase report assay and RNA pull-down experiments.ResultsIn this study, we observed that H19 was upregulated in SCLC compared with para-carcinoma tissues or NSCLC tissues. We also uncovered that H19 could promote proliferation and migration of SCLC cells. Functional investigation illustrated that H19 acted as a sponge for miR-140-5p to regulate its expression in SCLC. Interestingly, we further found that H19 upregulated FGF9 expression to promote SCLC progression via sponging miR-140-5p. H19 and FGF9 were also revealed to have similar expression patterns in clinical SCLC samples.ConclusionThese data demonstrated that H19 might be a promising prognostic and therapeutic target for SCLC.

MiR-665 Promotes the Biological Behavior of Small Cell Lung Cancer by Targeting LLGL1

背景与目的MicroRNAs（miRNAs）是一种广泛存在于真核生物体中的非编码小分子RNA，尽管一些miRNA在肿瘤中作用已被发现，但是miR-665对小细胞肺癌的中的表达及影响还尚不清楚。本研究旨在分析miR-665对肺癌细胞增殖、周期、侵袭和迁移的影响，探讨miR-665在小细胞肺癌中发挥的作用及其工作机制。方法qRT-PCR检测miR-665在肺癌组织和癌旁正常组织中的表达水平；TargetScan预测miR-665的潜在靶基因并用双荧光素酶报告基因实验、qRT-PCR和Western blot进行验证；免疫组化、qRT-PCR和Western blot检测LLGL1在肺癌组织和癌旁正常组织中的表达水平；CCK8法、流式细胞法、Transwell和细胞划痕实验检测miR-665和LLGL1对肺癌细胞NCI-H446、NCI-H1688增殖、侵袭、迁移以及S期细胞比值的影响；构建肺癌裸鼠移植瘤模型并观察miR-665对小鼠肿瘤生长的影响。结果miR-665在肺癌组织中的表达水平明显高于癌旁正常组织；miR-665能靶向作用于LLGL1的3’-UTR并抑制其表达；相比于癌旁正常组织，LLGL1在肺癌组织中的表达水平明显降低；抑制miR-665的表达可以抑制肺癌NCI-H446细胞的增殖、S期细胞比值、侵袭和迁移能力，而干扰LLGL1能逆转这种抑制效果；上调miR-665则促进肺癌NCI-H1688的增殖、S期细胞比值、侵袭和迁移能力，但这种促进效果同样被LLGL1的过表达逆转；在肺癌裸鼠移植瘤模型中，抑制miR-665能上调LLGL1蛋白的表达并抑制肿瘤的生长，而上调miR-665的表达则可以产生相反的结果。结论miR-665表达水平的变化与肺癌密切相关，miR-665可以通过抑制其靶基因LLGL1的表达促进肺癌细胞的生物学行为，在小细胞肺癌中发挥促癌基因的作用。

High expression of AKR1C1 is associated with proliferation and migration of small-cell lung cancer cells.

AKR1C1 is a member of the AKR1C family, which not only plays an important role in hormone metabolism but is believed to be involved in carcinogen metabolism. Our previous study demonstrated that AKR1C1 was highly expressed in lung tumor tissues as compared with the tumor-adjacent tissues. Small-cell lung cancer (SCLC) is a special type of lung cancer. Surgical treatment of SCLC is usually difficult due to the high degree of malignancy and early metastasis, and difficulty in obtaining clinical specimens. There is not much basic or clinical research on SCLC in the People’s Republic of China even in recent years. To investigate the mechanism of AKR1C1 in the pathogenesis of SCLC, the present study used H446 cell line to see whether AKR1C1 could affect the proliferation or migration of SCLC cells, and used a lentivirus to build the AKR1C1 overexpression and under-expression cell lines. The results indicated that AKR1C1 was an important inducement in the proliferation and migration of H446 cells. AKR1C1 promoted cell proliferation and played a vital role in the migration of SCLC cells. These results were also verified in nude mice in vivo. In conclusion, AKR1C1 plays an important role in the development and progression of SCLC and may represent an independent biomarker for assessment of the primary prognosis and therapy of SCLC.

N-acetylglucosaminyltransferase V modulates radiosensitivity and migration of small cell lung cancer through epithelial-mesenchymal transition.

N-acetylglucosaminyltransferase V (Gnt-V) has been linked to the migration of various human cancers. Recently we have found that inhibition of Gnt-V increases the radiosensitivity of cancer cells. However, the mechanisms by which Gnt-V mediates radiosensitivity and migration, especially in small cell lung cancer (SCLC) remain unknown. In our study, two SCLC cell lines (H1688 and H146) were used to investigate whether Gnt-V modulated the radiosensitivity and migration of SCLC cells through the epithelial-mesenchymal transition (EMT). The results showed that the expression of Gnt-V correlated with the N stage in patients with SCLC. Overexpression of Gnt-V led to a further increase in the relative viable cell number and survival fraction with a decrease in apoptosis rate and Bax/Bcl-2 ratio, when the cells were treated with irradiation. By contrast, knockdown of Gnt-V with irradiation resulted in a further decrease in the relative viable cell number and survival fraction but an increase in apoptosis rate and Bax/Bcl-2 ratio. Cells expressing high levels of Gnt-V increased migration whereas low levels of Gnt-V suppressed cell migration. Besides, the transient knockdown of ZEB2 led to an increase in radiosensitivity and an inhibition in the migration of SCLC cells. Furthermore, Gnt-V was negatively correlated with E-cadherin expression but positively correlated with N-cadherin, vimentin and ZEB2 expression. Finally, an in vivo study revealed that upregulation of Gnt-V caused tumour growth more quickly, as well as the expression of EMT-related markers (N-cadherin, vimentin and ZEB2). Taken together, the study suggested that an elevation of Gnt-V could lead to the radiosensitivity and migration of SCLC cells by inducing EMT, thereby highlighting Gnt-V as a potential therapeutic target for the prevention of EMT-associated tumour radioresistance and migration.