MicroRNA-185 suppresses proliferation, invasion, migration, and tumorigenicity of human prostate cancer cells through targeting androgen receptor

Previous studies have shown that androgen receptor (AR) is involved in the progression of prostate cancer (CaP) by several mechanisms. However, how AR is regulated has not been fully understood. In this study, miR-185 was found to be down-regulated in clinical CaP samples. Targets prediction revealed that AR had putative complementary sequences to miR-185, which was confirmed by the following dual luciferase reporter assay. Overexpression of miR-185 could reduce the expression of AR protein but not mRNA in LNCaP cells. The proliferation of LNCaP cells was inhibited by overexpression of miR-185. Cell cycle analysis revealed cell cycle arrest at G0/G1 phase. The invasive and migration abilities of cells could also be suppressed by miR-185. Furthermore, miR-185 inhibited tumorigenicity in a CaP xenografts model. CDC6, one target of AR and an important regulatory molecule for cell cycle, was found to be down-regulated by overexpression of miR-185. Our findings suggest that miR-185 could function as a tumor-suppressor gene in CaP by directly targeting AR, and act as a potential therapeutic target for CaP.     

miR-335 suppresses migration and invasion by targeting ROCK1 in osteosarcoma cells

Dynamic remodeling of the actin cytoskeleton is crucial for biological processes such as cell migration and cell spreading. S100A10 is a member of the S100 protein family and is involved in intracellular trafficking and cell migration. In this study, we examined the role of S100A10 in actin cytoskeletal organization and cell spreading. Depletion of S100A10 induced disruption of stress fiber formation and delay in cell spreading. Rac1 activation during spreading was suppressed by S100A10 knockdown, and exogenous expression of active Rac1 restored the ability of cells to spread in the absence of S100A10. Our results demonstrate the crucial role of S100A10 in actin dynamics promoting cell spreading via Rac1 activation.     

MicroRNA-1296-5p suppresses the proliferation,migration, and invasion of human osteosarcoma cells by targeting NOTCH2

Osteosarcoma (OS) is a highly aggressive bone tumor with a poor prognosis. MicroRNAs are revealed to exerts essential roles in the carcinogenesis and tumor invasion of OS. But, the function of miR-1296-5p and its related mechanism in OS progression have not yet been studied. This study discovered the levels of miR-1296-5p in OS and corresponding noncancerous tissues, and we demonstrated that miR-1296-5p level was markedly downregulated in tumor specimens as compared with nontumor tissues. In addition, we discovered that miR-1296-5p was also underexpressed in OS cells compared with the hFOB1.19 osteoblast cells. Interestingly, the reduced expression of miR-1296-5p was confirmed to associated with large tumor size, advanced tumor stages, and distance metastasis, respectively. Patients with OS low-expressing miR-1296-5p showed a prominent shorter survival. In addition, gain-of-function assays verified that miR-1296-5p overexpression remarkably repressed OS cell proliferation, migration, and invasion. Conversely, depletion of miR-1296-5p facilitated the growth and mobility of OS cells. Notably, miR-1296-5p inversely modulated notch receptor 2 (NOTCH2) in OS cells. The level of NOTCH2 messenger RNA was negatively correlated with miR-1296-5p level in OS samples. NOTCH2 knockdown markedly suppressed the abilities of MG-63 cell proliferation and mobility. More importantly, the restoration of NOTCH2 prominently rescued miR-1296-5p-induced tumor-suppressive effects on MG-63 cells. In conclusion, our study identified the reduced expression of miR-1296-5p, which contributed to OS progression. miR-1296-5p might be a promising prognostic marker and therapeutic target in OS.     

Retracted: MicroRNA-204-3p represses colon cancer cells proliferation,migration, and invasion by targeting HMGA2

Colon cancer is a detrimental neoplasm of the digestive tract. MicroRNAs (miRNAs) as central regulators have been discovered in colon cancer. Nonetheless, the impact of miR-204-3p on colon cancer remains indistinct. The research attempted to uncover the impacts of miR-204-3p on colon cancer cells growth, migration, and invasion. miR-204-3p expression level in colon cancer tissues and diverse colon cancer cell lines were testified by the quantitative real-time polymerase chain reaction. Exploration of the impacts of miR-204-3p on cell growth, migration, invasion, and their associated factors through assessment of CCK-8, flow cytometry, Transwell, and western blot, respectively. High mobility group AT-hook 2 (HMGA2) expression was then detected in Caco-2 cells after miR-204-3p mimic and inhibitor transfection, additionally dual-luciferase activity was implemented to further uncover the correlation between HMGA2 and miR-204-3p. The impact of HMGA2 on Caco-2 cell growth, migration, and invasion was finally assessed. We found that repression of miR-204-3p was discovered in colon cancer tissues and HCT116, SW480, Caco-2, HT29 and SW620 cell lines. MiR-204-3p overexpression mitigated Coca-2 cell viability, facilitated apoptosis, simultaneously adjusted CyclinD1 and cleaved caspase-3 expression. Cell migration, invasion, and the associated factors were all suppressed by miR-204-3p overexpression. Reduction of HMGA2 was presented in Caco-2 cells with miR-204-3p mimic transfection, and HMGA2 was predicated to be a target gene of miR-204-3p. Besides, HMGA2 silence showed the inhibitory effect on Caco-2 cells growth, migration, and invasion. In conclusion, miR-204-3p repressed colon cancer cell growth, migration, and invasion through targeting HMGA2.     

MicroRNA-144 inhibits hepatocellular carcinoma cell proliferation,invasion and migration by targeting ZFX

MicroRNA 144 (miR-144), a small non-coding RNA, is frequently dysregulated in human several tumour progression, but its role and the underlying mechanisms in hepatocellular carcinoma (HCC) is poorly investigated. In the present study, the expression of miR-144 was firstly analysed in datasets derived from GSE21362 and TCGA, and then detected in HCC tissues and cell lines by quantitative RT-PCR (qRT-PCR) analysis. MiR-144 was shown to be significantly down-regulated in HCC tissues and cell lines. Subsequently, overexpression of miR-144 was transfected into HCC cell lines so as to investigate its biological function, including MTT, colony formation, and transwell assays. Gain of function assay revealed miR-144 remarkably inhibited cell proliferation, migration and invasion. In addition, bioinformatical analysis and luciferase reporter assay identified ZFX as a novel target of miR-144 in HCC cells, as confirmed by qRT-PCR and Western blot. Furthermore, ZFX was found to be significantly up-regulated using Oncomine database analysis. Loss of function assay further indicated knockdown of ZFX had similar effects of miR-144-mediated HCC cell proliferation and invasion. Therefore, miR-144 has been demonstrated to act as a tumour suppressor in HCC cell growth and motility by directly targeting ZFX, which implicates its potential applications in the development of HCC treatment.     

miR-30a suppresses breast cancer cell proliferation and migration by targeting Eya2

Eye absent (Eya) proteins are involved in cell fate determination in a broad spectrum of cells and tissues. Aberrant expression of Eya2 has been documented in a variety of cancers and correlates with clinical outcome. However, whether microRNAs (miRNAs) can regulate Eya2 expression remains unknown. Here, we show that miR-30a represses Eya2 expression by binding to the 3′-untranslated region of Eya2. Overexpression of Eya2 in miR-30a-transfected breast cancer cells effectively rescued the inhibition of cell proliferation and migration caused by miR-30a. Knockdown of Eya2 by small-interfering RNA (siRNA) in breast cancer cells mimicked the effect induced by miR-30a and abolished the ability of miR-30a to regulate breast cancer cell proliferation and migration. The miR-30a/Eya2 axis could regulate G1/S cell cycle progression, accompanied by the modulation of expression of cell cycle-related proteins, including cyclin A, cyclin D1, cyclin E, and c-Myc. Moreover, miR-30a expression was downregulated in breast cancer patients, and negatively correlated with Eya2, which was upregulated in breast cancer patients. These data suggest that the miR-30a/Eya2 axis may play an important role in breast cancer development and progression and that miR-30a activation or Eya2 inhibition may be a useful strategy for cancer treatment.     

MicroRNA-193b modulates proliferation, migration, and invasion of non-small cell lung cancer cells

MicroRNAs have been reported to be closely related to the development of human lung cancers. However, the functions of microRNAs in non-small cell lung cancer (NSCLC) remain largely undefined. Here, we investigated the role of microRNA-193b (miR-193b) in NSCLC. Our data showed that miR-193b was markedly down-regulated in NSCLC cancer tissues compared with adjacent normal tissues. The NSCLC cell line (A549) transfected with the miR-193b exhibited significantly decreased proliferation, migration, and invasion capacities when compared with the control cells. In contrast, inhibition of miR-193b increased the proliferation, migration, and invasion of A549 cells. Moreover, miR-193b repressed the expressions of cyclin D1 and urokinase-type plasminogen activator in A549 cells. These data suggest that miR-193b is a tumor suppressor in NSCLC.     

MicroRNA-29a suppresses the growth,migration, and invasion of lung adenocarcinoma cells by targeting carcinoembryonic antigen-related cell adhesion molecule 6

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an important regulator of cell adhesion, invasion, and metastasis. The aim of this study was to evaluate the functional roles of CEACAM6 in lung adenocarcinoma and to identify miRNAs that inhibit the growth, migration, and invasion of lung adenocarcinoma cells by targeting CEACAM6. CEACAM6 expression is associated with poor prognosis of patients with lung adenocarcinoma, and CEACAM6 has important functional roles in controlling the growth, migration, and invasion of lung adenocarcinoma cells in vitro and in vivo. Furthermore, miR-29a can suppress the growth, migration, and invasion of lung adenocarcinoma cells by targeting CEACAM6. Therefore, miR-29a/CEACAM6 axis represents a potential therapeutic target for treatment of lung adenocarcinoma.     

miR-342-3p suppresses proliferation,migration and invasion by targeting FOXM1 in human cervical cancer

FOXM1 is a well-established oncogenic factor that has been reported to be involved in multiple biological processes including cell proliferation, growth, angiogenesis, migration and invasion. It can also be regulated by miRNAs. In this study, we reported that FOXM1 is directly targeted by miR-342-3p, which is down-regulated along with its host gene, EVL, in human cervical cancer tissues compared to the adjacent normal tissues. Functional studies suggested that the overexpression of miR-342-3p inhibits cell proliferation, migration and invasion in cervical cell lines. FOXM1 is upregulated and negatively correlates with miR-342-3p in cervical cancer tissues, and the overexpression of FOXM1 rescues the phenotype changes induced by the overexpression of miR-342-3p.     

MicroRNA-320a inhibits cell proliferation,migration and invasion by targeting BMI-1 in nasopharyngeal carcinoma

In the present study, we investigated the roles and molecular mechanisms of miR-320a in human nasopharyngeal carcinoma (NPC). miR-320a expression was strongly reduced in NPC tissues and cell lines. Overexpression of miR-320a significantly suppressed NPC cell growth, migration, invasion and tumor growth in a xenograft mouse model. A luciferase reporter assay revealed that miR-320a could directly bind to the 3′ UTR of BMI-1. Overexpression of BMI-1 rescued miR-320a-mediated biological function. BMI-1 expression was found to be up-regulated and inversely correlated with miR-320a expression in NPC. Collectively, our data indicate that miR-320a plays a tumor suppressor role in the development and progression of NPC and may be a novel therapeutic target against NPC.     

MicroRNA-212 suppresses nonsmall lung cancer invasion and migration by regulating ubiquitin-specific protease-9

MicroRNAs (miRNAs) play crucial roles in various biological processes, including migration, proliferation, differentiation, cell cycling, and apoptosis. Epithelial-mesenchymal transition (EMT) has been shown to be related to the capability of migration and invasion in many tumor cells. In this study, we used wound-healing assay and transwell invasion to analysis the capability of migration and invasion in non–small-cell lung carcinoma (NSCLC), respectively. The expression of ubiquitin-specific protease-9-X-linked (USP9X) and miR-212 messenger RNA (mRNA) was determined by quantitative real-time polymerase chain reaction and Western blot analysis was used to determine the E-cadherin and vimentin expression. Our results showed that miR-212 mimic inhibited cell migration and invasion, while miR-212 inhibitor increased cell migration and invasion. There was no significant difference between WP1130 and miR-212 mimic combined with WP1130 groups. Moreover, WP1130 inhibited the capability of the migration and invasion of NSCLC cells. Western blot analysis displayed that miR-212 mimic upregulated E-cadherin expression and downregulated vimentin expression, while miR-212 inhibitor downregulated E-cadherin and upregulated vimentin expression. These data showed that miR-212 regulated NSCLC cell invasion and migration by regulating USP9X expression. Taken together, these findings indicated that miR-212 regulated NSCLC cells migration and invasion through targeting USP9X involved in EMT.     

Overexpression LINC01082 suppresses the proliferation,migration and invasion of colon cancer

The active form of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)₂D₃), was reported to improve vascular function in patients with diabetes, yet the underlying mechanisms remain to be fully elucidated. Monoamine oxidase (MAO), a mitochondrial enzyme, with two isoforms (A and B) that generates hydrogen peroxide (H₂O₂) as by-product, has been recently reported to contribute to the pathogenesis of endothelial dysfunction in diabetes. The present study assessed the interaction between vitamin D and MAO in the vascular wall in the setting of type 1 experimental diabetes. To this aim, diabetes was induced in male Wistar rats via a single injection of streptozotocin (STZ, 50 mg/kg, IP) and 1 month later thoracic aortas were harvested and used for organ bath studies and H₂O₂ measurements. MAO expression was assessed by immunohistochemistry and RT-PCR. Endothelial function was evaluated in isolated aortic rings in the absence vs. presence of 1,25(OH)₂D₃ (100 nM, 24 h incubation). In diabetic animals, we found a significant reduction in the endothelial-dependent relaxation to acetylcholine and an increased expression of the MAO-A isoform, respectively. Vitamin D significantly improved vascular function, mitigated oxidative stress and decreased MAO-A expression in diabetic vascular preparations. In conclusion, MAO-A is induced in diabetic aortas and vitamin D can improve diabetes-induced endothelial dysfunction by modulating the MAO-A expression.

     

Downregulation of microRNA-92b-3p suppresses proliferation,migration, and invasion of gastric cancer SGC-7901 cells by targeting Homeobox D10

To investigate the effect and mechanism of microRNA-92b-3p (miR-92b-3p) targeting Homeobox D10 (HOXD10) on proliferation, migration, and invasion of gastric cancer, we detected t he expression of miR-92b-3p and HOXD10 in SGC-7901 cells. The effects of miR-92b-3p or HOXD10 on proliferation, migration, invasion, and matrix metalloproteinase (MMP)-2/9 expression in SGC-7901 cells were measured by the Cell Counting Kit-8 assay, Transwell assay, and Western blot, respectively. The results showed that miR-92b-3p expression was increased, and HOXD10 expression was decreased in SGC-7901 cells, compared with human normal gastric epithelial cells GES-1. Functional experiments demonstrated that cell proliferation, migration, invasion, and expression of MMP-2/9 in SGC-7901 cells were significantly inhibited by miR-92b-3p silencing and HOXD10 overexpression. Moreover, HOXD10 was a potential target gene of miR-92b-3p as evidenced by the TargetScan software and double luciferase reporter assay. In the rescue experiment, knockdown of HOXD10, accompanied by higher expression of MMP-2/9, could significantly eliminate the inhibitory effects of miR-92b-3p silencing on cell proliferation, migration, and invasion. In conclusion, miR-92b-3p is highly expressed in gastric cancer SGC-7901 cells, and interfering with its expression might inhibit SGC-7901 cell proliferation, migration, and invasion via downregulating MMP-2/9 expression and targeting HOXD10.