Retracted: MicroRNA-145 performs as a tumor suppressor in human esophageal squamous cell carcinoma by targeting phospholipase C epsilon 1

Esophageal squamous cell carcinoma (ESCC) is the leading pathologic type in China. miR-145 has been reported to be downregulated in multiple tumors. This study was aimed to investigate the role of miR-145 in ESCC. miR-145 expression was investigated in 65 ESCC samples as well as four ESCC cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Targetscan 6.2 website ( http://www.targetscan.org/ ) was used to predict the targets of miR-145. Expression of phospholipase C epsilon 1 (PLCE1) messenger RNA and protein was detected by qRT-PCR or Western blot. MTT and wound healing assay were conducted to explore the effects of miR-145 on the proliferation and migration of ESCC cell lines, respectively. miR-145 was significantly decreased in ESCC tissues. An inverse correlation between miR-145 and invasion depth and TNM stage were observed. PLCE1 was a direct target of miR-145, and the expression of PLCE1 was inversely correlated with miR-145 expression in ESCC tissues. In addition, overexpression of miR-145 suppressed cell proliferation and migration in ESCC cells. The enforced expression of PLCE1 partially reversed the suppressive effect of miR-145. These results prove that miR-145 may perform as a tumor suppressor in ESCC by targeting PLCE1.     

MiR-526b targets lncRNA SLC16A1-AS1 to suppress cell proliferation in triple-negative breast cancer

The present study investigated the potential interaction between miR-526b and lncRNA SLC16A1-AS1 in triple-negative breast cancer (TNBC). Expression of miR-526b and SLC16A1-AS1 in TNBC tumor tissues and paired nontumor tissues from 60 TNBC patients was detected by real-time polymerase chain reaction (RT-qPCR). The interaction between miR-526b and SLC16A1-AS1 was evaluated with overexpression experiments, followed by RT-qPCR. The proliferation and migration of cells were detected with cell counting kit-8 assay and Transwell assay, respectively. Apoptosis of cells was assessed by cell apoptosis assay. The expression of apoptosis-related proteins was quantified by Western blot analysis. MiR-526b was predicted to bind with SLC16A1-AS1. Overexpression of miR-526b in TNBC cells decreased the expression levels of SLC16A1-AS1, while overexpression of SLC16A1-AS1 did not affect the expression of miR-526b. In TNBC tissues, miR-526b was downregulated in TNBC tissues, while SLC16A1-AS1 was upregulated in TNBC tissues compared to that in nontumor tissues. The expression of SLC16A1-AS1 and miR-526b were inversely correlated. In vitro experiments showed that overexpression of SLC16A1-AS1 promoted cell proliferation and invasion but suppressed cell apoptosis. MiR-526b played an opposite role and suppressed the function of SLC16A1-AS1. MiR-526b is downregulated in TNBC and it targets SLC16A1-AS1 to regulate proliferation, apoptosis, and invasion of TNBC cells.     

Long noncoding RNA HAND2-AS1 inhibits cancer cell proliferation,migration, and invasion in esophagus squamous cell carcinoma by regulating microRNA-21

Long noncoding RNA (lncRNA) HAND2-AS1 is a well-characterized tumor suppressor in several types of malignancies, while its role in esophagus squamous cell carcinoma (ESCC) is unknown. In this study, we found that lncRNA HAND2-AS1 was downregulated, while microRNA-21 ( miRNA-21) was upregulated in tumor tissues than in adjacent healthy tissues of ESCC patients. Expression levels of lncRNA HAND2-AS1 and miRNA-21 were significantly and inversely correlated in tumor tissues but not in healthy tissues. Plasma levels of lncRNA HAND2-AS1 were lower in ESCC patients than in healthy controls, and downregulation of plasma lncRNA HAND2-AS1 distinguished early stage ESCC patients from healthy controls. lncRNA HAND2-AS1 overexpression resulted in downregulation of miRNA-21 in cells of ESCC cell lines and inhibited cell proliferation, migration, and invasion. miRNA-21 overexpression failed to affect lncRNA HAND2-AS1 expression but significantly attenuated the inhibitory effect of lncRNA HAND2-AS1 overexpression on cancer cell proliferation, migration, and invasion. Therefore, lncRNA HAND2-AS1 may inhibit cancer cell proliferation, migration, and invasion in ESCC by regulating miRNA-21.     

LncRNA PAPAS promotes hepatocellular carcinoma by interacting with miR-188-5p

It has been observed that long noncoding RNA (lncRNA) PAPAS regulates rRNA synthesis, but its role in human diseases is unclear. Our study was carried out to investigate the role of PAPAS in hepatocellular carcinoma (HCC). In the present study, we found that PAPAS was upregulated both in plasma from patients with HCC and tumors compared with plasma from healthy people and tumor-adjacent healthy tissues. Expression levels of PAPAS in tumor tissues and plasma of patients with HCC were significantly and positively correlated. Plasma levels of PAPAS effectively distinguished stage I patients from healthy controls. MicroRNA (miR)-188-5p was downregulated in tumor tissues than in tumor-adjacent healthy tissues of patients with HCC, and was inversely correlated with PAPAS in tumor tissues but not in adjacent healthy tissues. PAPAS and miR-188-5p downregulated each other. PAPAS overexpression promoted, while miR-188-5p overexpression inhibited the HCC cell proliferation. Rescue experiment showed that miR-34a overexpression attenuated the effects of PAPAS overexpression. However, PAPAS overexpression failed to affect significantly cancer cell migration and invasion. Therefore, lncRNA PAPAS promotes HCC by interacting with miR-188-5p.     

LncRNA PTCSC3 inhibits triple-negative breast cancer cell proliferation by downregulating lncRNA H19

Long noncoding RNA (lncRNA) PTCSC3 (hereafter PTCSC3 is used to represent lncRNA PTCSC3) inhibits glioma and thyroid cancer, indicating its potential tumor suppression function in other types of cancers. We explored the potential involvement of PTCSC3 in triple-negative breast cancer (TNBC). In the current study, we found that PTCSC3 was downregulated in tumor tissues of patients with TNBC. PTCSC3 expression was positively correlated with plasma levels of PTCSC3. LncRNA H19 was upregulated and was inversely correlated with PTCSC3 in tumor tissues. PTCSC3 overexpression led to downregulated H19 in TNBC cells, while H19 overexpression did not affect PTCSC3 expression. PTCSC3 inhibited and H19 promoted proliferation of TNBC cells. H19 overexpression attenuated the effects of PTCSC3 overexpression. Cancer cell migration and invasion were not significantly affected by PTCSC3 overexpression. Therefore, lncRNA PTCSC3 inhibits TNBC cell proliferation by downregulating lncRNA H19.     

Low miR-143/miR-145 Cluster Levels Induce Activin A Overexpression in Oral Squamous Cell Carcinomas,Which Contributes to Poor Prognosis

Deregulated expression of activin A is reported in several tumors, but its biological functions in oral squamous cell carcinoma (OSCC) are unknown. Here, we investigate whether activin A can play a causal role in OSCCs. Activin A expression was assessed by qPCR and immunohistochemistry in OSCC tissues. Low activin A-expressing cells were treated with recombinant activin A and assessed for apoptosis, proliferation, adhesion, migration, invasion and epithelial-mesenchymal transition (EMT). Those phenotypes were also evaluated in high activin A-expressing cells treated with follistatin (an activin A antagonist) or stably expressing shRNA targeting activin A. Transfections of microRNA mimics were performed to determine whether the overexpression of activin A is regulated by miR-143/miR-145 cluster. Activin A was overexpressed in OSCCs in comparison with normal oral mucosa, and high activin A levels were significantly associated with lymph node metastasis, tumor differentiation and poor survival. High activin A levels promoted multiple properties associated with malignant transformation, including decreased apoptosis and increased proliferation, migration, invasion and EMT. Both miR-143 and miR-145 were markedly downregulated in OSCC cell lines and in clinical specimens, and inversely correlated to activin A levels. Forced expression of miR-143 and miR-145 in OSCC cells significantly decreased the expression of activin A. Overexpression of activin A in OSCCs, which is controlled by downregulation of miR-143/miR-145 cluster, regulates apoptosis, proliferation and invasiveness, and it is clinically correlated with lymph node metastasis and poor survival.     

Long noncoding RNA lnc-ABCA12-3 promotes cell migration,invasion, and proliferation by regulating fibronectin 1 in esophageal squamous cell carcinoma

Long noncoding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). We previously demonstrated that a novel lncRNA, lnc-ABCA12-3, was overexpressed in ESCC tissues. However, the exact function of lnc-ABCA12-3 is unknown. In the current study, we aimed to evaluate the expression of lnc-ABCA12-3 in ESCC and to explore the potential mechanism of lnc-ABCA12-3 in cell migration, invasion, and proliferation. We showed that lnc-ABCA12-3 was upregulated in ESCC tumor tissues and cell lines. The increased expression of lnc-ABCA12-3 was positively associated with advanced tumor-node-metastasis stages and poor prognosis. The knockdown of lnc-ABCA12-3 inhibited the cell migration, invasion, and proliferation abilities of KYSE-510 and Eca-109 cells. We also found that fibronectin 1 (FN1) was upregulated in ESCC tumor tissues. The expression of FN1 messenger RNA was positively correlated with the expression of lnc-ABCA12-3 in ESCC tumor tissues. After lnc-ABCA12-3 knockdown, the expression of FN1 was downregulated. In addition, the overexpression of FN1 restored the abilities of cell migration, invasion and proliferation in Eca-109 cells. Further studies indicated that lnc-ABCA12-3 acted as a competing endogenous RNA for miR-200b-3p to regulate FN1 expression. In conclusion, these results suggest that lnc-ABCA12-3 is a novel oncogene in tumorigenesis and that its high expression is related to a poor prognosis for patients with ESCC. lnc-ABCA12-3 promotes cell migration, invasion, and proliferation via the regulation of FN1 in ESCC. Our data suggest that lnc-ABCA12-3 might serve as a potential prognostic biomarker and therapeutic target for ESCC.     

miR-760 exerts an antioncogenic effect in esophageal squamous cell carcinoma by negatively driving fat metabolism via targeting c-Myc

miR-760 is downregulated in various human tumors, and fat metabolism disorder correlates with tumor progression, especially anomalism of key fat metabolic enzymes that are positively modulated by c-Myc. The aim of our study is to elucidate the presumptive molecular mechanisms of miR-760-mediated esophageal squamous cell carcinoma (ESCC) cell function and to assess the therapeutic significance of miR-760 in ESCC patients. Quantitative real-time PCR (RT-qPCR) analysis indicated that miR-760 was significantly downexpressed in ESCC tissues and cell lines. Cell counting kit-8 (CCK-8) assay, colony formation assay, transwell assay, and flow cytometry denoted that induced ectopic overexpression of miR-760 dramatically inhibited ESCC cells proliferation, attenuated migration, and invasion facilitated apoptosis in vitro. Mechanistically, c-Myc predicted using bioinformatics was identified as a potential target gene of miR-760 by luciferase reporter assay. Furthermore, mRNA and protein expression levels of c-Myc and key fat metabolic enzymes were downregulated with miR-760 mimics. The above investigation results, responsible for the antineoplastic properties of miR-760 in ESCC, preliminarily highlighted that the hypothetical signal amongst miR-760, c-Myc, and key fat metabolic enzymes may develop a novel diagnostic marker, therapeutic target, and independent prognostic indicator.     

Long noncoding RNA LINC-PINT is inhibited in gastric cancer and predicts poor survival

Long noncoding RNA (lncRNA) LINC-PINT expression is inhibited in many types of cancer cells, suggesting its role as a tumor suppressor. However, the functionality of LINC-PINT in gastric cancer and the clinical values are unknown. In the present study, we found that lncRNA LINC-PINT was downregulated, while microRNA-21 (miR-21) was upregulated in tumor tissues than in adjacent healthy tissues of gastric cancer patients. A significant and inverse correlation between expression levels of lncRNA LINC-PINT and miR-21 was found in both tumor tissues and adjacent healthy tissues. The low expression level of LINC-PINT and high expression level of the miR-21 tumor were correlated with poor prognosis. LINC-PINT overexpression casued miR-21 inhibition in cells of human gastric cancer cell lines, while miR-21 overexpression did not alter LINC-PINT expression. LINC-PINT overexpression led to inhibited, while miR-21 overexpression led to promoted proliferation, migration, and invasion of gastric cancer cells. Effects of LINC-PINT overexpression on cellular behaviors of gastric cancer cells were attenuated by miR-21 overexpression. Therefore, LINC-PINT may participate in gastric cancer through the crosstalk with miR-21.     

Elevation of long non-coding RNA GAS5 and knockdown of microRNA-21 up-regulate RECK expression to enhance esophageal squamous cell carcinoma cell radio-sensitivity after radiotherapy

ObjectiveLately, lncRNAs have been proposed to function in the radio-sensitivity of tumor cells, yet the role of lncRNA GAS5 in that of esophageal squamous cell carcinoma (ESCC) has scarcely been studied. This study aims to examine GAS5's effects on ESCC cell radio-sensitivity.MethodsGAS5, miR-21 and RECK expression in radiation-sensitive and radiation-resistant ESCC tissues, and TE-1 and TE-1-R cells was determined. TE-1 and TE-1-R cells were treated with pcDNA-GAS5 or miR-21 inhibitors to figure out their roles in ESCC cell proliferation, radio-sensitivity, and apoptosis via gain- and loss-of-function experiments.ResultsWe found underexpressed GAS5 and RECK, and overexpressed miR-21 in ESCC. GAS5 elevation and miR-21 inhibition reduced viability and the colony formation ability, and enhanced the apoptosis of ESCC cells under radiation.ConclusionOur study reveals that GAS5 elevation up-regulates RECK expression by down-regulating miR-21 to increase ESCC cell apoptosis after radiation therapy, thus enhancing cell radio-sensitivity.     

Reduced LINC00551 expression promotes proliferation and invasion of esophageal squamous cancer by increase in HSP27 phosphorylation

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and long noncoding RNAs (lncRNAs) regulate gene expression or activities. This study investigated the role of lncRNA LINC00551 in ESCC development and progression. Three paired ESCC and normal tissues were subjected to next‐generation sequencing and we identified 82 upregulated and 60 downregulated lncRNAs, including LINC00551, which was confirmed to markedly downregulated in 78 ESCC tissues and in the Gene Expression Profiling Interactive Analysis data set. Downregulated LINC00551 expression was associated with lymph node metastasis, advanced TNM stage, and tumor size. Moreover, downregulated LINC00551 expression was also associated with poor progression‐free survival and overall survival of ESCC patients. In vitro and in vivo, LINC00551 overexpression inhibited ESCC cell proliferation and invasion, whereas knockdown of LINC00551 expression promoted ESCC cell proliferation and invasion. RNA pull‐down and mass spectrometry assays identified the potential LINC00551 binding proteins, and HSP27 was a promising LINC00551 targeting proteins after RNA immunoprecipitation assay. At the protein level, LINC00551 bound to and decreased HSP27 phosphorylation, and in turn, downregulated ESCC cell proliferation and invasion. The current study demonstrated the functional significance of LINC00551 in ESCC development, progression, and prognosis. Further study will assess LINC00551 as a novel prognostic marker or therapeutic target for ESCC.     

The lncRNA small nucleolar RNA host gene 5 regulates trophoblast cell proliferation,invasion, and migration via modulating miR-26a-5p/N-cadherin axis

Pre-eclampsia (PE) is a pregnancy-specific disease characterized by the occurrence of hypertension and proteinuria after two weeks of gestation. Long noncoding RNAs (lncRNAs) are emerging as key regulators in PE development. This study aims to investigate the role of lncRNA, small nucleolar RNA host gene 5 (SNHG5), in the pathogenesis of PE. The expression of SNHG5 was significantly downregulated in placental tissues from patients with severe PE compared normal controls. Overexpression of SNHG5 promoted trophoblast (HTR-8/SVneo) cell proliferation, invasion, and migration, and flow cytometry results showed that SNHG5 overexpression inhibited apoptosis and caused a decrease of cell population at the G ₀/G ₁ phase and an increase of cell population at the S phase, while knockdown of SNHG5 had the opposite effects. The interaction between SNHG5 and miR-26a-5p was predicted by bioinformatics analysis and confirmed by luciferase reporter assay and RNA immunoprecipitation, and miR-26a-5p was negatively regulated by SNHG5; miR-26a-5p expression was upregulated in PE placental tissues and was inversely correlated with SNHG5 expression. Furthermore, miR-26a-5p was predicted to target the 3′ untranslated region of N-cadherin, which was confirmed by luciferase reporter assay, and miR-26a-5p overexpression suppressed N-cadherin expression in HTR-8/SVneo cells. N-cadherin mRNA expression was downregulated in PE placental tissues and was positively correlated with SNHG5 expression. Both overexpression of miR-26a-5p and knockdown of N-cadherin suppressed HTR-8/SVneo cell invasion and migration, and also attenuated the effects of SNHG5 on the cellular functions of HTR-8/SVneo cells. In conclusion, our study suggested that SNHG5 promotes trophoblast cell proliferation, invasion, and migration at least partly via regulating the miR-26a-5p/N-cadherin axis.     

LncRNA POU3F3 promotes proliferation and inhibits apoptosis of cancer cells in triple-negative breast cancer by inactivating caspase 9

It has been reported that lncRNA POU3F3 was upregulated in esophageal squamous-cell carcinomas, indicating its role as an oncogene in this disease. However, the mechanism of its function and its involvement in other malignancies is unknown. In the present study we found that expression levels of lncRNA POU3F3 were higher in tumor tissues than in adjacent healthy tissues of triple negative breast cancer (TNBC) patients and were significantly and inversely correlated with levels of cleaved caspase 9 only in tumor tissues. In addition, plasma levels of lncRNA POU3F3 were higher in TNBC patients than in healthy controls and were significantly and inversely correlated with levels of cleaved caspase 9 only in TNBC patients. In addition, treatment of exogenous Cleaved Caspase-9 significantly attenuated the effects of lncRNA POU3F3 overexpression on cancer cell proliferation and apoptosis. lncRNA POU3F3 may promote proliferation and inhibit apoptosis of cancer cells in triple-negative breast cancer.