Retracted: MicroRNA-34a inhibit hepatocellular carcinoma progression by repressing hexokinase-1

Hepatocellular carcinoma (HCC) is known as a frequent type of primary cancer in the liver, and it is the third-most common cause of cancer-related death all over the world. However, the molecular mechanism in the progression of HCC is still unclear. The current study was designed to investigate the expression and function of microRNA-34a (miR-34a) in HCC. In HCC tissues and cells, the expression levels of miR-34a were analyzed by quantitative real-time polymerase chain reaction. The association between the level of miR-34a and hexokinase (HK)-1 was also investigated via luciferase reporter assay. Cell viability and proliferation were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. To assess whether miR-34a can limit tumor growth in vivo, animal models and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used for examining the role of miR-34a on the development of HCC and cell apoptosis. The expression level of miR-34a was reduced in HCC samples and cells. The expression of miR-34a was associated with the viability and proliferation capacity of HCC cells, and miR-34a could inhibit HCC cells proliferation by inhibiting HK1. In the mouse model of HCC, volumes and weight of the tumors were significantly decreased by transfection with miR-34a mimic compared with the control group. Furthermore, miR-34a mimics could induce apoptosis in a greater proportion of cells compared with the control group. Taken together, the data may provide some novel insights into the molecular mechanism of miR-34a and HK1 in the progression of HCC. Thus, miR-34a/HK1 axis might be a novel promising therapeutic target for treating HCC.     

Interleukin-1β/nuclear factor-κB signaling promotes osteosarcoma cell growth through the microRNA-181b/phosphatase and tensin homolog axis

So far, microRNA has attracted plenty of interest due to its role in tumorigenesis. Reportedly, miR-181b may be involved in the tumorigenesis of osteosarcoma (OS). In the current study, we attempted to investigate the detailed function and mechanism of miR-181b in OS carcinogenesis. Herein, miR-181a, miR-181b, miR-181c, and miR-181d expressions in OS tissues were higher than that in nontumor tissue samples as examined real-time polymerase chain reaction. Via direct targeting, miR-181b negatively regulated the expression of phosphatase and tensin homolog (PTEN), a well-known tumor suppressor. Furthermore, a small interfering RNA strategy was used to find that interleukin (IL)-1B and nuclear factor-κB (NF-κB) regulate miR-181b and PTEN expression. Consequently, the repression of PTEN by miR-181b promotes OS cell proliferation. In summary, our data support a critical role for NF-κB-dependent upregulation of miR-181b, which further inhibited PTEN expression and promoted the cell proliferation of OS cell lines. The above findings represent a new pathway for the repression of PTEN and the promotion of cell proliferation upon IL-1β induction.     

MiR-134-5p attenuates neuropathic pain progression through targeting Twist1

Neuropathic pain is a kind of chronic pain because of dysfunctions of somatosensory nerve system. Recently, many studies have demonstrated that microRNAs (miRs) play crucial roles in neuropathic pain development. This study was designed to investigate the effects of miR-134-5p on the process of neuropathic pain progression in a rat model established by chronic sciatic nerve injury (CCI). First, we observed that miR-134-5p was significantly decreased in CCI rat models. Overexpression of miR-134-5p strongly alleviated neuropathic pain behaviors including mechanical and thermal hyperalgesia. Meanwhile, inflammatory cytokine expression, such as IL-6, IL-1β and TNF-α in CCI rats were greatly repressed by upregulation of miR-134-5p. Twist1 has been widely regarded as a poor prognosis biomarker in diverse diseases. Here, by using bioinformatic analysis, 3′-untranslated region (UTR) of Twist1 was predicted to be a downstream target of miR-134-5p in our study. Here, we found that overexpression of miR-134-5p was able to suppress Twist1 dramatically. Furthermore, it was exhibited that Twist1 was increased in CCI rats time-dependently and Twist1 was inhibited in vivo. Subsequently, downregulation of Twist1 in CCI rats could depress neuropathic pain progression via inhibiting neuroinflammation. In conclusion, our current study indicated that miR-134-5p may inhibit neuropathic pain development through targeting Twist1. Our findings suggested that miR-134-5p might provide a novel therapeutic target for neuropathic pain.     

Suppressive effect of exogenous miR-16 and miR-34a on tumorigenesis of breast cancer cells

Recent investigations have shown tumor-suppressive roles for miR-16 and miR-34a. They also share some features in regard to targeting cancer cell signaling pathways which they control. Therefore, in this study, we aimed to further scrutinize whether exogenous induction of mature miR-34a and miR-16 can collaborate in breast tumor suppression. MDA-MB-231 and SK-BR-3 human breast cancer cell lines were cultured and transfected twice with hsa-miR-16-5p and hsa-miR-34a-5p mimics individually or in combination. The cells were analyzed for apoptosis rate and cell cycle indices by flow cytometry. Also, the expression of several invasion and the epithelial-mesenchymal transition markers was evaluated at gene and protein levels by quantitative real-time polymerase chain reaction and western blot analysis, respectively. Assessment of invasiveness and migratory potential of the transfected cells was performed using three-dimensional spheroid formation and wound-healing assay, respectively. In both cell lines, miR-16 and miR-34a induced apoptosis and cell-cycle arrest and also suppressed invasion and migration. Some of these effects, like cell-cycle arrest and induction of apoptosis, were significantly higher when using both microRNAs than when using them individually for transfection of the cells. Our results are indicating that miR-16 and miR-34a can collaborate in breast tumor suppression.     

Retracted: Upregulation of long noncoding RNA TUG1 contributes to the development of laryngocarcinoma by targeting miR-145-5p/ROCK1 axis

Laryngocarcinoma is the most common head and neck cancer and has a high incidence and mortality, causing about 83 000 deaths per year worldwide. Our research aimed to investigate the possible role of long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in laryngocarcinoma development. The messenger RNA (mRNA) levels of TUG1 in tumor tissues and control (plasma) samples of laryngocarcinoma patients as well as in laryngocarcinoma cells were detected. The influences of TUG1 suppression on cell biological processes (viability, apoptosis, migration, and invasion) and cytoskeleton rearrangement in laryngocarcinoma cells were tested. Moreover, we investigated the regulatory interaction between TUG1 and miR-145-5p, and identified the target gene of miR-145-5p. The association between TUG1 and the protein expressions of RhoA/rho associated coiled-coil containing protein kinase (ROCK)/matrix metalloproteinases (MMPs) pathway-associated factors were detected. TUG1 was found to be highly expressed in tumor tissues and plasma samples of laryngocarcinoma patients as well as in laryngocarcinoma cells. Suppression of TUG1 decreased laryngocarcinoma cell viability, increased apoptosis, and suppression migration, invasion, and cytoskeleton rearrangement. Moreover, TUG1 negatively regulated miR-145-5p. TUG1 regulated tumor growth (viability and apoptosis) and metastasis through miR-145-5p. Furthermore, ROCK1 was targeted by miR-145-5p, and miR-145-5p/ROCK1 partner was involved in the process of tumor growth and metastasis. Finally, we found that TUG1 functioned on laryngocarcinoma by activating RhoA/ROCK/MMPs pathway. Our study reveals that lncRNA TUG1 is upregulated in laryngocarcinoma and may be involved in the process of laryngocarcinoma through miR-145-5p downregulation and activating the RhoA/ROCK/MMPs signals.     

MicroRNA-424 regulates epithelial-mesenchymal transition of endometrial carcinoma by directly targeting insulin-like growth factor 1 receptor

Although numerous miRNAs are reported to contribute to the carcinogenesis of malignant tumor, the specific role of miR-424 in endometrial carcinoma is seldom reported. To explore the effect of miR-424 on epithelial-mesenchymal transition and its underlying mechanism, we detected miR-424 expression in endometrial carcinoma tissue and cells. We found that miR-424 was significantly downregulated in endometrial carcinoma tissues and cells, especially in HEC-1B cells. To perform the functional analysis, we transfected HEC-1B with miR-424-mi, miR-424-inh, mi-control, and inh-control, respectively. We found that overexpression of miR-424 significantly decreases cell proliferation and migration, accompanied with the increased E-cadherin/Vimentin expression and the transition of mesenchymal to epithelial cell phenotype. We identified that insulin-like growth factor-1 receptor (IGF-1R) was a potential target of miR-424 by computational analysis followed by luciferase reporter assays. Of note, we found that the downregulation of miR-424 in HEC-1B cells enhanced endogenous IGF-1R expression. Further mechanistic analysis revealed that forced expression of IGF-1R in miR-424-mim transfected cells remedied the weakened migration resulting from overexpression of IGF-1R. Taken together, the results of the current study demonstrated that miR-424 was a tumor suppressor for endometrial carcinoma and a favorable factor against tumor progression through targeting IGF-1R, thus providing a target for the treatment of endometrial carcinoma.     

NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in macrophages through inhibiting miR-128

Long noncoding RNAs (lncRNA) have been recognized as significant regulators in the progression of atherosclerosis (AS). Oxidized low-density lipoprotein (ox-LDL) can induce macrophage inflammation and oxidative stress, that serves important roles in AS. However, the exact function of lncRNA NEAT1 and its possible molecular mechanism in AS remain unclear. Here, we concentrated on the roles and molecular mechanisms of NEAT1 in AS development. In our current study, we observed that NEAT1 was elevated by ox-LDL in a dose-dependent and time-dependent manner. RAW264.7 cell survival was greatly enhanced, and cell apoptosis was significantly inhibited by LV-shNEAT1 transfection. In addition, knockdown of NEAT1 in RAW264.7 cells repressed CD36 expression and foam cell formation while NEAT1 overexpression shown an opposite process. Moreover, NEAT1 downregulation inhibited inflammation molecules including IL-6, IL-1β, and TNF-α. Meanwhile, silencing of NEAT1 can also suppress reactive oxygen species (ROS) and malondialdehyde (MDA) levels with an enhancement of superoxide dismutase (SOD) activity in RAW264.7 cells. MicroRNAs are some short RNAs, and they can regulate multiple biological functions in many diseases including AS. Here, we found that miR-128 expression was remarkably decreased in ox-LDL-incubated RAW264.7 cells. Interestingly, miR-128 mimics was able to reverse AS-correlated events induced by overexpression of NEAT1. By using bioinformatics analysis, miR-128 was predicted as a target of NEAT1 and the correlation between them was validated in our study. Taken these together, it was implied that NEAT1 participated in ox-LDL-induced inflammation and oxidative stress in AS development through sponging miR-128.     

Inhibition of miR146b-5p suppresses CT-guided renal cell carcinoma by targeting TRAF6

Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system. Due to the lack of early symptoms, diagnosis of RCC usually occurs at late stages or after cancer metastasis leading to poor prognosis. Therefore, it is crucial to study early molecular mechanisms and biomarkers. Previous studies have suggested that microRNAs are involved in RCC initiation and development, making them a good candidate for early diagnosis and therapy. MiR146b-5P plays important roles in the progression of multiple cancers including thyroid cancer, pancreatic cancer, cervical cancer. However, it is not clear whether and how miR146b-5P is involved in RCC. In this study, we aimed to investigate the function of miR146b-5P in RCC. We examined the expression levels of miR146b-5p in renal cancer tissue and cell lines. We also explored the effects of blocking miR146b-5p in renal tumor growth and inflammatory signaling. Finally, we determined if miR146b-5p regulates tumorigenesis through TRAF6. We found that miR146b-5p levels were significantly increased in renal cancer tissue and renal cancer cells. Blocking miR146b-5p suppressed renal tumor growth and enhanced inflammatory response through increased TRAF6 expression. These effects were eliminated in TRAF6 knockout mice. Our results suggest that enhanced miR146b-5p expression may be a biomarker for RCC and modulating miR146b-5p and TRAF6 levels represent a potential therapeutic strategy for RCC.     

Retracted: miR-145 modulates epithelial-mesenchymal transition and invasion by targeting ZEB2 in non–small cell lung cancer cell lines

Lung cancer is the leading cause of cancer-related deaths worldwide. Epithelial-mesenchymal transition (EMT) is a major event that drives cancer progression. Here we aim to investigate the role of microRNA, miR-145, in regulating EMT of the highly invasive non–small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction analysis indicated that miR-145 was downregulated in cancer tissue compared with that in adjacent normal tissue. NSCLC cell lines, namely H1299, PC7, and SPCA-1, also demonstrated miR-145 downregulation, which is correlated well with their invasive ability, assessed by the Matrigel invasion assay. miR-145 overexpression resulted in downregulation of N-cadherin, and downregulation of vimentin and E-cadherin, suggesting a decreased EMT activity. TargetScan analysis predicted that a binding site exists between miR-145 and an oncogene, ZEB2, which was verified using the dual-luciferase assay. Alteration of miR-145 expression also induced inverse effects on ZEB2 expression, and a negative correlation exists between ZEB2 and miR-145 in human tissues. ZEB2 and miR-145 also exerted antagonizing effects on the invasion of NSCLC cells. Therefore, miR-145 is an important molecule in NSCLC that regulates cancer EMT through targeting ZEB2.