Inhibition of lncRNA KCNQ1OT1 Improves Apoptosis and Chemotherapy Drug Response in Small Cell Lung Cancer by TGF-β1 Mediated Epithelial-to-Mesenchymal Transition / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required. @*Materials and Methods@#In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance. @*Results@#The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells. @*Conclusion@#Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

Role of TGF-β1 in multi-drug resistance in small cell lung cancer and its clinical significance / 中南大学学报(医学版)

Objective:To investigate the role of transforming growth factor β1 (TGF-β1) in multi-drug resistance in small cell lung cancer and its clinical significance.Methods:The mRNA and protein expressions of TGF-β 1 in H69 and H69AR cells were detected by real-time PCR and Western blot,respectively.After silence of TGF-[β1,the sensitivity of H69AR to drugs was detected by CCK8 assay.The expressions of TGF-β1 in lung cancer and paracarcinoma tissues were examined by QRT-PCR and immunohistochemistry.The relationship of TGF-β 1 expression with clinical pathological features and prognosis of patients was studied.Results:Compared to H69,the mRNA and protein expressions of TGF-β1 in H69AR cells were significantly increased by (5.93±0.47) and (8.49±1.92) folds,respectively (P＜0.01).Transfection ofTGF-β1 siRNA resulted in a decrease of TGF-β1 expression by 70.432％ in H69AR ceils (F=21.20,P＜0.01) and an increase insensitivity to chemotherapeutic agents of H69AR cells (t=4.576,P＜0.05).Compare with the paracarcinoma tissues,the expression of TGF-β1 was significantly increased in small cell lung cancer tissues (t=13.925,P＜0.01),which was closely related with clinical stage,chemosensitivity and overall survival (all P＜0.05),but not related with gender,age (both P＞0.05).Conclusion:TGF-β1 is involved in the regulation of small cell lung cancer multidrug resistance,which may be a potential marker to evaluate the chemosensitivity and dinical prognostic for small cell lung cancer.

Expression of miR-139-5p in small cell lung cancer tissue and its clinical significance / 吉林大学学报(医学版)

Objective:To explore the expression of miR-139-5p in small cell lung cancer (SCLC)tissue and its clinical significance, and to clarify the role of miR-139-5p in the occurrence and development of SCLC. Methods:The biological function of miR-139-5p was examined by cell growth,apoptosis and cell cycle analysis. The expressions of miR-139-5p in 50 cases of cancer tissue and paracarcinoma normal tissue were examined by QRT-PCR.Combined with the clinical data,the role of miR-139-5p in clinic was anzlyzed.Results:The expression level of miR-139-5p in SCLC tumor tissue was lower than that in normal lung tissue (P 0.05).The expression level of miR-139-5p in the patient at LD stage was lower than that of the patients at ED stage (P <0.01).The expression level of miR-139-5p in the resistant patients was higher than that of the patients sensitive to chemotherappy (P <0.01).The expression level of miR-139-5p in the survival patients was lower than that in the death patients (P <0.01).Cox regression analysis indicated that miR-139-5p expression and disease stage were the independent prognostic factors for SCLC.Conclusion:miR-139-5p in participates in the occurrence and development of SCLC by inhibiting the cell proliferation,promoting apoptosis and inducing the cell cycle arrest;it may be used as a target gene to evaluate the prognosis of SCLC patients.

Role of SALL4 in regulating multi-drug resistance of small cell lung cancer and its clinical significance / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the role of SALL4 in regulating multi-drug resistance in small cell lung cancer (SCLC), and to evaluate its clinical significance.</p><p><b>METHODS</b>The expression of SALL4 protein and gene was detected by Western blot and real-time PCR (RT-PCR) in both H69 and H69AR cell lines, respectively. SALL4 expression in H69AR was blocked by the siRNA, and then the drug-sensitivities of H69AR cell lines to chemotherapeutic drugs such as cisplatin, doxorubicin, and etoposide were evaluated by cell counting kit assay. SALL4 expression was also examined by immunohistochemistry, and correlated with patients' clinicopathological features and prognosis.</p><p><b>RESULTS</b>The expression of SALL4 was significantly increased in H69AR cells than in the H69 cells (P < 0.01). Down-regulation of SALL4 increased the drug-sensitivities of H69AR cells to chemotherapeutic drugs (P = 0.02). The expression of SALL4 was significantly increased in SCLC than in para-carcinoma tissues (P < 0.01). SALL4 expression correlated with clinical stage, chemosensitivity and overall survival (P < 0.05), but not with patients' age and gender.</p><p><b>CONCLUSION</b>SALL4 is involved in the regulation of multidrug resistance in SCLC; SALL4 may be a potential target gene to evaluate the chemosensitivity and clinical prognosis for SCLC.</p>

Expression of nucleolar spindle-associated protein 1 in hepatocellular carcinoma and its clinical significance / 中华肝胆外科杂志

Objective To investigate the expression of nucleolar spindle-associated protein 1(NuSAP1) in hepatocellular carcinoma (HCC) and in non-cancerous tissues,and to study the correlation between NuSAP1 and early recurrence and prognosis of HCC.Methods The expression of NuSAP1 in 61 cases of HCC and non-cancerous tissues were assessed by RT-PCR,quantitative PCR and immunohistochemistry.The relationship between the expression and the clinicopathological features was studied.Results The levels of mRNA and protein in HCC were higher than the non-cancerous tissues (P＜0.05).On univariate analysis,the expression levels of NuSAP1,mRNA and protein in HCC were significantly associated with TNM classification,lymphatic metastasis,early recurrence,tumor thrombosis and histological differentiation (P＜0.05).Multivariate analysis showed early recurrence was associated with the expression of NuSAP1 protein in HCC (P＜0.05).Overexpression of NuSAP1 protein was correlated with poor outcome of the patients with HCC (x2=15.846,P＜0.001).Conclusions NuSAP1 was overexpressed in hepatocellular carcinoma.Overexpression of NuSAP1 was associated with early postoperative HCC recurrence and bad prognosis.