MEG3 LncRNA from Exosomes Released from Cancer-Associated Fibroblasts Enhances Cisplatin Chemoresistance in SCLC via a MiR-15a-5p/CCNE1 Axis.

PURPOSE: Long non-coding RNAs (lncRNAs) may act as oncogenes in small-cell lung cancer (SCLC). Exosomes containing lncRNAs released from cancer-associated fibroblasts (CAF) accelerate tumorigenesis and confer chemoresistance. This study aimed to explore the action mechanism of the CAF-derived lncRNA maternally expressed gene 3 (MEG3) on cisplatin (DDP) chemoresistance and cell processes in SCLC. MATERIALS AND METHODS: Quantitative real-time PCR was conducted to determine the expression levels of MEG3, miR-15a-5p, and CCNE1. Cell viability and metastasis were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide and invasion assays, respectively. A xenograft tumor model was developed to confirm the effect of MEG3 overexpression on SCLC progression in vivo. Relationships between miR-15a-5p and MEG3/CCNE1 were predicted using StarBase software and validated by dual luciferase reporter assay. Western blotting was used to determine protein levels. A co-culture model was established to explore the effects of exosomes on MEG3 expression in SCLC cell lines. RESULTS: MEG3 was overexpressed in SCLC tissues and cells. MEG3 silencing significantly repressed cell viability and metastasis in SCLC. High expression of MEG3 was observed in CAF-derived conditioned medium (CM) and exosomes, and promoted chemoresistance and cancer progression. Additionally, MEG3 was found to serve as a sponge of miR-15a-5p to mediate CCNE1 expression. Overexpression of miR-15a-5p and knockout of CCNE1 reversed the effects of MEG3 overexpression on cell viability and metastasis. CONCLUSION: MEG3 lncRNA released from CAF-derived exosomes promotes DDP chemoresistance via regulation of a miR-15a-5p/CCNE1 axis. These findings may provide insight into SCLC therapy.

Retraction Note: Diagnostic and prognostic value of plasma microRNA-195 in patients with non-small cell lung cancer.

This article [1] is retracted at the request of Editor-in-Chief due to overlap with articles [2-5].None of the authors have responded to any correspondence from the editor or publisher about this retraction.

Long noncoding RNA H19 mediated the chemosensitivity of breast cancer cells via Wnt pathway and EMT process.

BACKGROUND: Breast cancer is still one of the major public health burdens worldwide, although there is tremendous progress in early diagnosis and treatment of breast cancer. Tamoxifen was one of the most popular endocrine therapies for early-stage estrogen receptor (ER) + breast cancer patients. However, a high incidence of drug resistance develops along with poor prognosis in breast cancer. Currently, long noncoding RNAs (lncRNAs) are emerging and are well suited to play a role in the development of cancer and tamoxifen resistance. However, there is little reported about the relationship of breast cancer resistance to tamoxifen and lncRNA H19. Here, we validated that lncRNA H19 was highly expressed in breast cancer especially in patients with late stage (III and IV), compared to normal tissues and early stage cancers (I and II). METHODS: Quantitative polymerase chain reaction (qPCR) was utilized for comparison of lncRNA H19 expression level in breast cancers with different stages. qPCR and Western blotting were used to detect gene and protein, respectively. RESULTS: We found that lncRNA H19 expression level manipulated breast cancer cell proliferation both in parental breast cancer cell lines and tamoxifen-resistant cell lines. Knockdown of lncRNA H19 elevated tamoxifen sensitivity for promoting cell growth and inhibiting apoptosis in tamoxifen-resistant breast cancer cells. Moreover, knockdown of H19 inhibited Wnt pathway and epithelia-mesenchymal transition in tamoxifen-resistance breast cancer cells. CONCLUSION: Taken together, the results of this study provided the evidence for H19 in regulating tamoxifen-resistant breast cancer and might provide novel options in the future treatment of tamoxifen-resistance breast cancer patients.

Diagnostic and prognostic value of plasma microRNA-195 in patients with non-small cell lung cancer.

BACKGROUND: Recently, circulating microRNAs (miRNAs) have been reported to be stably detectable in plasma/serum and to function as potent biomarkers in various cancers. The aim of this study was to evaluate the expression level of plasma miRNA-195 in patients with non-small cell lung cancer (NSCLC) and investigate its diagnostic and prognostic value. METHODS: Quantitative real-time PCR was performed to evaluate plasma miRNA-195 levels in 100 NSCLC patients and 100 healthy volunteers. The association between miRNA-195 expression and clinicopathological factors as well as the overall survival was analyzed. Receiver-operating characteristic (ROC) curve analysis was carried out to assess the potential value of plasma miRNA-195 for NSCLC diagnosis. RESULTS: Plasma miRNA-195 was downregulated in NSCLC patients compared with healthy controls (P < 0.001). Decreased plasma miRNA-195 expression was significantly associated with lymph node metastasis and advanced clinical stage. ROC curve analysis showed that plasma miRNA-195 was a useful marker for NSCLC diagnosis. Multivariate Cox regression analysis confirmed low plasma miRNA-195 expression as an independent unfavorable prognostic factor for NSCLC patients. CONCLUSIONS: These findings indicate that plasma miRNA-195 might serve as a promising biomarker for the early detection and prognosis evaluation of NSCLC.