Long noncoding RNA LINC00339 promotes laryngeal squamous cell carcinoma cell proliferation and invasion via sponging miR-145

Laryngeal squamous cell carcinoma (LSCC) is a very common neoplasm of the head and neck in the world. Long noncoding RNAs play key roles in cell infiltration, fate, apoptosis, and invasion. However, the functional role and expression of LINC00339 remains unclear in LSCC. In this study, we showed that the expression level of LINC00339 was upregulated in LSCC tissues and cell lines. LINC00339 silencing suppressed the proliferation, invasion, and epithelial-mesenchymal transition (EMT) progression of LSCC cells. In addition, we showed that LINC00339 acted as a sponge of miR-145, and LINC00339 silencing promoted the expression of miR-145 in Hep2 cell. Furthermore, the expression of miR-145 was lower in LSCC tissues than in their paired normal samples and the miR-145 expression level was negatively correlated with LINC00339 expression in LSCC tissues. The knockdown of miR-145 promoted the proliferation, invasion, and EMT progression of LSCC cells. Finally, we indicated that LINC00339 silencing inhibited the proliferation, invasion, and EMT progression of LSCC cells by suppressing the miR-145 expression. These data suggested that LINC00339 acted as an oncogene in the development of LSCC, partly by regulating the miR-145 expression.     

Long noncoding RNA LINC00968 promotes endothelial cell proliferation and migration via regulating miR-9-3p expression

Long noncoding RNAs (lncRNAs) have been showed to play a crucial role in pathogenesis and development of cardiovascular diseases. Our study aimed to study the expression and functional role of lncRNA LINC00968 in the development of coronary artery disease (CAD). We showed that the LINC00968 expression level was upregulated in the CAD tissues compared with normal arterial tissues. In addition, we showed that the expression level of LINC00968 was upregulated by oxidized low-density lipoprotein (oxLDL) treatment in endothelial cell. Ectopic expression of LINC00968 regulated the proliferation and migration of endothelial cell. Moreover, we showed that overexpression of LINC00968 inhibited miR-9-3p expression in an endothelial cell. Furthermore, we demonstrated that the miR-9-3p expression was downregulated in the CAD samples compared with normal arterial tissues and the expression level of miR-9-3p was downregulated by oxLDL treatment in endothelial cell. Finally, we showed that ectopic expression of LINC00968 promoted endothelial cell proliferation and migration partly through regulating miR-9-3p expression. These results suggested that LINC00968 plays a crucial role in the progression of the CAD.     

Long noncoding RNA LINC00346 promotes glioma cell migration,invasion and proliferation by up‐regulating ROCK1

Long noncoding RNAs have key roles in glioma progression. However, the function and mechanisms of action of the long noncoding RNA, LINC00346, in glioma remain unclear. In our study, we observed that LINC00346 levels were increased in glioma tissue samples, and according to Gene Expression Profiling Interactive Analysis, its levels were related to disease‐free survival and overall survival rates, suggesting that a high level of LINC00346 expression corresponds to a poor prognosis. We next confirmed the high levels of LINC00346 expression in glioma tissues and cell lines and showed that LINC00346 knockdown suppressed glioma cell proliferation, migration and invasion; promoted apoptosis; and delayed tumour growth. Moreover, the oncogenic function of LINC00346 may be explained, in part, by the down‐regulation of miR‐340‐5p and the de‐repression of ROCK1. We showed that LINC00346 may function as a competing endogenous RNA of miR‐340‐5p, thereby de‐repressing ROCK1. This study revealed a new regulatory network in glioma and identified potential therapeutic targets for this cancer.     

LINC01433 promotes hepatocellular carcinoma progression via modulating the miR-1301/STAT3 axis

Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in hepatocellular carcinoma (HCC) tumor progression. LINC01433 has been implicated in the progression of lung cancer. However, its biological role in HCC remains poorly understood. In our current study, we focused on the detailed mechanism of LINC01433 in HCC development. First, it was exhibited that LINC01433 was remarkably elevated in HCC cells, which indicated that LINC01433 was involved in HCC. Then, knockdown of LINC01433 was able to restrain HCC cell proliferation and cell colony formation and greatly induced cell apoptosis. On the contrary, overexpression of LINC01433 promoted HCC cell proliferation, increased cell colony formation, and enhanced cell invasion capacity. Subsequently, we found that miR-1301 was remarkably decreased in HCC cells, and it can serve as a target of LINC01433 according to bioinformatics analysis. In addition, the binding correlation between them was validated by performing RNA pull-down experiments and RIP assay. Moreover, STAT3 was predicted and validated as a target of miR-1301, and it was shown that miR-1301 mimics significantly suppressed STAT3 in HCC cells. Finally, in vivo models were established, and the results demonstrated that silencing of LINC01433 could repress HCC development through modulating miR-1301 and STAT3. Taken together, these results indicated in our study that LINC01433 participated in HCC progression through modulating the miR-1301/STAT3 axis and it might act as a novel biomarker in HCC diagnosis and treatment.     

LncRNA MALAT1/miR‐129 axis promotes glioma tumorigenesis by targeting SOX2

We aimed to explore the interaction among lncRNA MALAT1, miR‐129 and SOX2. Besides, we would investigate the effect of MALAT1 on the proliferation of glioma stem cells and glioma tumorigenesis. Differentially expressed lncRNAs in glioma cells and glioma stem cells were screened out with microarray analysis. The targeting relationship between miR‐129 and MALAT1 or SOX2 was validated by dual‐luciferase reporter assay. The expressions of MALAT1, miR‐129 and SOX2mRNA in both glioma non‐stem cells and glioma stem cells were examined by qRT‐PCR assay. The impact of MALAT1 and miR‐129 on glioma stem cell proliferation was observed by CCK‐8 assay, EdU assay and sphere formation assay. The protein expression of SOX2 was determined by western blot. The effects of MALAT1 and miR‐129 on glioma tumour growth were further confirmed using xenograft mouse model. The mRNA expression of MALAT1 was significantly up‐regulated in glioma stem cells compared with non‐stem cells, while miR‐129 was significantly down‐regulated in glioma stem cells. MALAT1 knockdown inhibited glioma stem cell proliferation via miR‐129 enhancement. Meanwhile, miR‐129 directly targeted at SOX2 and suppressed cell viability and proliferation of glioma stem cells by suppressing SOX2 expression. The down‐regulation of MALAT1 and miR‐129 overexpression both suppressed glioma tumour growth via SOX2 expression promotion in vivo. MALAT1 enhanced glioma stem cell viability and proliferation abilities and promoted glioma tumorigenesis through suppressing miR‐129 and facilitating SOX2 expressions.     

LncRNA Linc00511 promotes osteosarcoma cell proliferation and migration through sponging miR-765

Long noncoding RNA (lncRNA) Linc00511 is a novel lncRNA, and it was reported to play important roles in the progression and carcinogenesis of several tumors. However, the expression and biological roles of Linc00511 in osteosarcoma were still unknown. In this research, we showed that the expression of Linc00511 was upregulated in osteosarcoma samples and cell lines. Ectopic expression of Linc00511 promoted osteosarcoma cell growth, colony formation, and migration. Moreover, overexpression of Linc00511 enhanced the epithelial-mesenchymal transition progression in osteosarcoma cell. In addition, we showed that elevated expression of Linc00511 suppressed microRNA-765 (miR-765) expression and promoted apurinic/apyrimidinic endonuclease 1 (APE1) expression in osteosarcoma cell. The expression of miR-765 was downregulated in osteosarcoma cells and samples and was negatively related to Linc00511 expression in osteosarcoma tissues. Ectopic expression of miR-765 inhibited osteosarcoma cell growth and migration. Furthermore, we showed that Linc00511 overexpression promoted MG-63 cells proliferation, colony formation, and migration via downregulation of miR-765. These results suggested that Linc00511 played as an oncogene in the development of osteosarcoma.     

Silencing LINC00491 inhibits prostate cancer development through the miR-384/TRIM44 axis

Accumulating evidence has demonstrated the key role of long noncoding (lnc)RNAs in tumorigenesis. Prostate cancer (PCa) is a cancer with high mortality that requires further exploration of the underlying molecular mechanisms. In the present study, we aimed to discover novel potential biomarkers for diagnosing PCa and targeting treatment. Overexpression of the lncRNA, LINC00491, was verified in PCa tumor tissues and cell lines using the real-time polymerase chain reaction. Cell proliferation and invasion were then analyzed via the Cell Counting Kit-8, colony formation, and transwell assays in vitro, and tumor growth in vivo. The interaction of miR-384 with LINC00491, as well as TRIM44, was investigated via bioinformatics analyses, subcellular fractionation, luciferase reporter gene assays, radioimmunoprecipitation, pull-down, and western blot analyses. LINC00491 was overexpressed in PCa tissues and cell lines. LINC00491 knockdown resulted in impaired cell proliferation and invasion in vitro and decreased tumor growth in vivo. Moreover, LINC00491 acted as a sponge for miR-384 and its downstream target, TRIM44. Additionally, miR-384 expression was downregulated in PCa tissues and cell lines, and its expression was negatively correlated with LINC00491. A miR-384 inhibitor restored the inhibitory effects of LINC00491 silencing on PCa cell proliferation and invasion. LINC00491 is a tumor promoter in PCa via enhancing TRIM44 expression by sponging miR-384 to facilitate the development of PCa. LINC00491 plays a significant role in PCa and could serve as both a biomarker for early diagnosis and a novel treatment target.     

Retracted: Long non-coding RNA LINC00152 promotes cell growth and invasion of papillary thyroid carcinoma by regulating the miR-497/BDNF axis

Long intergenic non-coding RNA 152 (LINC00152) was reported to be tightly linked to tumorigenesis and progression in multiple cancers. However, its biological role and modulatory mechanism in papillary thyroid carcinoma (PTC) has not been elucidated. In this study, we determined the expression levels of LINC00152 in PTC tissues and cell lines by quantitative real time polymerase chain reaction (qRT-PCR). Cell proliferation, colony formation, migration, and invasion were measured by a Cell Counting Kit-8 assay, colony formation analysis, wound healing, and transwell invasion assay, respectively. A luciferase reporter assay and qRT-PCR were used to determine whether LINC00152 interacts with miR-497 directly. We established a xenograft mouse model to examine the underlying molecular mechanism and effect of LINC00152 on tumor growth in vivo. We found that LINC00152 expression was significantly increased in PTC tissues and derived cell lines. LINC00152 knockdown significantly inhibited proliferation, colony formation, migration, and invasion in vitro, and impaired tumor growth in vivo. We revealed that LINC00152 functioned as a competing endogenous RNA to the miR-497 sponge, downregulating its downstream target brain-derived neurotrophic factor (BDNF), which is an oncogene in thyroid cancer. These findings suggest that LINC00152 is responsible for PTC cell proliferation and invasion and exerts its function by regulating the miR-497/BDNF axis.     

LncRNA H19/miR-194/PFTK1 axis modulates the cell proliferation and migration of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge due to its high mortality and morbidity; gene therapy might be a promising treatment for PDAC. The critical role of Wnt-signaling pathway in cancer pathogenesis has been widely recognized; cyclin-dependent kinase 14 (CDK14, PFTK1)-induced low-density lipoprotein receptor-related proteins 5/6 (LRP5/6) phosphorylation is an important issue in Wnt-signaling activation. Long noncoding RNA (LncRNA)-microRNA (miRNA)-messenger RNA (mRNA) modulating the pathogenesis of cancers has been regarded as a major mechanism. In the current study, upregulated lncRNAs positively correlated with PFTK1 were analyzed and selected using The Cancer Genome Atlas (TCGA) database. Of them, lncRNA H19 can activate Wnt signaling in cancers. In PDAC tissues, the expression of H19 and PFTK1 were upregulated; H19 knockdown suppressed the cell proliferation and migration of PDAC, while PFTK1 overexpression partially attenuated the suppressive effect of H19 knockdown. As analyzed by TCGA and predicted by online tools, miR-194 was negatively correlated with PFTK1 and might bind to both H19 and PFTK1, which was further confirmed by luciferase reporter and RNA immunoprecipitation assays. Moreover, the effect of H19 knockdown on PFTK1 protein and the cell proliferation and migration could be partially reversed by miR-194 inhibition; H19/miR-194 axis modulated PDAC cell proliferation and migration through PFTK1 downstream Wnt signaling. Results suggested that rescuing miR-194 expression in PDAC can inhibit lncRNA H19 and PFTK1 expression, subsequently suppressing PDAC cell proliferation and migration. Due to the complexity of the lncRNA-miRNA-mRNA network, further in vivo experiments examining potential side effects are needed in future study to explore the clinical application of these findings.     

Overexpression of Hsc70 promotes proliferation,migration, and invasion of human glioma cells

Migration and invasion are often recognized as the main reasons for the high recurrence and death rates of glioma and limit the efficacy of surgery and other antitumor therapies. In this study, we found over activation of heat shock cognate protein 70 (Hsc70) in human glioma specimens, which was closely related to glioma grade. We investigated whether Hsc70 induced the migration and invasion of glioma cells. Wound healing and transwell migration assay were used to determine the migration and invasion ability of human glioma U251 and U87 cells, in which the expression of Hsc70 was knocked down by small interfering RNA. Western blot analysis was performed to determine the expression of FAK-Src signaling in malignant glioma cells. The results showed that Hsc70 deficiency significantly retarded migration and invasion and reduced the phosphorylation of FAK, Src, and Pyk2 in U251 and U87 cells. Overall, our results indicate that the migration and invasion capacity of human brain glioma cells is at least partly induced by Hsc70-dependent activation of FAK-Src signaling.