A novel LINC00478 serves as a tumor suppressor in endometrial carcinoma progression.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in the pathogenesis and progression of various cancers, but their roles in endometrial cancer (EC) are largely unknown. METHODS: The expressions of LINC00478 and PTBP1 in EC tissues were determined by RT-qPCR. Cell counting kit-8, flow cytometry and Transwell assays were executed for detecting the roles of LINC00478 in EC cells proliferation, migration and invasion. The mouse-xenograft models were established by subcutaneous injection in vivo. The interaction between LINC00478 and PTBP1 was confirmed by RNA pull-down assay and RNA-binding protein immunoprecipitation assay. RESULTS: LINC00478 was significantly down-regulated in EC tissues while compared to that in their paracancerous samples, and a higher expression level of LINC00478 was negatively correlated with clinical progress of EC patients. Functional experiments in vivo and in vitro revealed that LINC00478 overexpression could dramatically retard the proliferation of EC cells, decrease the rate of colony formation, suppress the migration and invasion abilities of EC cells in vitro and inhibit tumor growth in vivo. Mechanistically, LINC00478 regulated the expression of PTBP1, a key factor in the Warburg effect, and affected the metabolic process of EC cells. CONCLUSIONS: LINC00478 acts as a tumor suppressor in EC by negatively controlling PTBP1 expression and influencing the Warburg effect, providing a potential biomarker and therapeutic target for patients with EC.

Identification of Three Circular RNA Cargoes in Serum Exosomes as Diagnostic Biomarkers of Non-Small-Cell Lung Cancer in the Chinese Population.

The recent discovery of circular RNAs (circRNAs) in serum exosomes suggests a novel and potentially useful tool for noninvasive cancer diagnosis. However, there are currently no substantial studies addressing this topic. RNA-sequencing analysis was performed between three pairs of non-small-cell lung cancer (NSCLC) patients and controls. The diagnostic values of exosomal circRNAs were assessed in a training set, validation set 1, and validation set 2. A total of 46 abnormally expressed circRNAs were identified. Among these, circ_0047921, circ_0056285, and circ_0007761 were found to display significant diagnostic validity for NSCLC. In distinguishing NSCLC cases from healthy controls, the panel of aforementioned circRNAs exhibited area under the curve (AUC) values of 0.926 (95% CI, 0.895-0.956) in the training set and 0.919 (95% CI, 0.877-0.962) in validation set 1. Circ_0047921 could distinguish NSCLC cases from chronic obstructive pulmonary disease controls (AUC, 0.890; 95%CI, 0.831-0.948), whereas the circ_0056285 and circ_0007761 combination could distinguish NSCLC cases from tuberculosis controls (AUC, 0.820; 95% CI, 0.739-0.902). For an early NSCLC diagnosis, similar results were observed for these circRNAs in distinguishing early-stage NSCLC cases from healthy controls, chronic obstructive pulmonary disease controls, or tuberculosis controls. Circ_0056285 expression was correlated with clinical stages and lymph node metastasis. The exosomal circRNAs, circ_0047921, circ_0056285, and circ_0007761, are promising biomarkers for NSCLC diagnosis in the Chinese population.

Down expression of lnc-BMP1-1 decreases that of Caveolin-1 is associated with the lung cancer susceptibility and cigarette smoking history.

Lnc-BMP1-1 is a lncRNA transcribed from SFTPC (surfactant associated protein C), a lung tissue specific gene encoding pulmonary-associated surfactant protein C (SPC) that is solely secreted by alveolar typeⅡ epithelial cells, among which the ones with SFTPC+ might be transformed into lung adenocarcinoma cells. Caveolin-1 (Cav-1) is a candidate tumor suppressor gene and is vital for coping with oxidative stress induced by cigarette smoke. When comparing lung cancer tissues with their adjacent normal tissues, the expression of lnc-BMP1-1 were decreased, especially in patients with cigarette smoking history (P=0.027), and positively associated with the expression of Cav-1 (P<0.001). When comparing to A549 cells transfected with empty vector (A549-NC cells), the expression level of Cav-1 in A549 cells with over-expressed lnc-BMP1-1 (A549-BMP cells) was increased along with the decreased level of HDAC2 protein. The drug sensitivity of A549-BMP cells to Doxorubicin hydrochloride (DOX) was increased; the growth and migration capability of A549-BMP cells were inhibited along with the decreased protein level of Bcl-2 and DNMT3a; the growth of tumor in nude mice injected with A549-BMP cells were inhibited, too. Furthermore, the lnc-BMP1-1 and Cav-1 expression was also down-regulated in the human bronchial epithelial (16HBE) cells treated with cigarette smoke extract (CSE).

Long Noncoding RNA PRRG4-4 Promotes Viability, Cell Cycle, Migration, and Invasion in Lung Cancer Cells.

There is a perception that long noncoding RNA (lncRNA) has relationship with carcinogenesis. Many studies have previously identified and validated that the section of chromosome 11p13 is associated with high incidence of tumor. In this study, we investigated a new lncRNA, named lncPRRG4-4, mapped to 11p13 and suspected that lncPRRG4-4 was a potential lung cancer-related gene. To explore its role in carcinogenesis, we first demonstrated that lncPRRG4-4 was upregulated in lung cancer tissues compared with adjacent nontumor tissues and functioned as an oncogene in lung cancer cells. The lncPRRG4-4 was significantly upregulated in lung cancer tissues compared with adjacent normal counterparts (mean ± standard deviation: 0.12 ± 0.84 vs. 0.05 ± 0.22; p < 0.001). Patients with metastasis exhibited high levels of lncPRRG4-4 expression than those without metastasis in both the southern samples (p = 0.045) and eastern samples (p = 0.030), total samples (p = 0.004). In addition, downregulation of lncPRRG4-4 expression inhibited lung cancer proliferation, viability, migration, and invasion ability, arrested cell cycle, facilitated apoptosis, and vice versa. Taken together, these observations suggested that the lncPRRG4-4 functions as an oncogene in lung cancer cells.

Upregulation of LncRNA FEZF-AS1 is associated with advanced clinical stages and family history of cancer in patients with NSCLC.

Antisense RNA (AS) is a type of long non-coding RNAs that functions as a post-transcriptional regulatory element on regulating parental coding gene expression via directly binding to complementary mRNA sequences. We aimed to investigate the effect of the AS to FEZF1 gene on non-small cell lung cancer (NSCLC) development. The expression level of lncRNA FEZF-AS1 and FEZF1 was determined by the quantitative Real-time PCR in 160 cases of NSCLC tissues and their adjacent non-tumour tissues. We found that lncRNA FEZF-AS1 was significantly up-regulated in tumour tissues when compared to the adjacent non-cancerous tissues (P = 0.001), and it's high expression correlated with advanced stages (P = 0.002) and Tumour Family History (P = 0.029). Meanwhile, In 58 cases of NSCLC tissues the expression of lncRNA FEZF-AS1 was positively associated with that of FEZF1expression (r = 0.8810, p = 1.6575E-20). By GEPIA database analysis, we also found that the expression of lncRNA FEZF-AS1 and FEZF1 were significantly higher in tumour tissues than those of the adjacent non-cancerous tissues in 969 NSCLC patients (P < 0.05), and lncRNA FEZF-AS1 was positively correlated with FEZF1 (r = 0.90, P < 0.001). These results suggest that lncRNA FEZF-AS1 relate to the progression of lung cancer patients and it may be a potential target for cancer therapy.