Silencing of lncRNA LINC00514 inhibits the malignant behaviors of papillary thyroid cancer through miR-204–3p/CDC23 axis

Numerous studies have provided that long noncoding RNAs (lncRNAs) possess important roles in regulating tumorigenesis. However, up to data, the role of LINC00514 in cancer, including thyroid cancer, remains unknown. In the present study, we found that LINC00514 expression was significantly upregulated in papillary thyroid cancer (PTC) tissues by bioinformatics analysis. Loss-of-function studies revealed that LINC00514 silencing inhibited the proliferation, migration and invasion of PTC cells while promoting apoptosis in vitro. Moreover, LINC00514 knockdown suppressed PTC growth in vivo. RNA-FISH showed that LINC00514 mainly locates in the nucleus of PTC cells. Through bioinformatics prediction, we identified that LINC00514 served as the sponge for miR-204–3p, and miR-204–3p directly targeted CDC23. Thus, LINC00514 promoted CDC23 expression via restraining miR-204–3p activity, leading to PTC progression. In sum, our findings demonstrated that LINC00514 contributes to PTC progression and might be a potential target for PTC therapy.     

LINC01303 functions as a competing endogenous RNA to regulate EZH2 expression by sponging miR‐101‐3p in gastric cancer

Long non‐coding RNA (lncRNA) is one of the important regulators of many malignancies. However, the biological function and clinical significance of a large number of lncRNAs in gastric cancer remain unclear. Therefore, we analysed the TCGA data to find that LINC01303 is significantly up‐regulated in gastric cancer tissues. However, the biological function of LINC01303 in GC remains unknown. In our study, we found that the expression of LINC01303 was significantly higher in GC tissues than in adjacent tissues by real‐time quantitative PCR. We can significantly inhibit the malignant proliferation, migration and invasion of GC cells by silencing LINC01303 expression. In addition, LINC01303 knockdown can also inhibit GC growth in vivo. After the bioinformatics analysis, we found that LINC01303 can be used as a miR‐101‐3p sponge to competitively adsorb miR‐101‐3p with EZH2. Therefore, our results indicate that LINC01303 promotes the expression of EZH2 by inhibiting miR‐101‐3p activity and promotes GC progression. In summary, in this study, we demonstrated for the first time that the LINC01303/miR‐101‐3p/EZH2 axis promotes GC progression.     

LINC00339 promotes gastric cancer progression by elevating DCP1A expression via inhibiting miR-377-3p

Up to date, the mechanism of gastric cancer (GC) development is poorly understood. This study was to demonstrate the effects of LINC00339 on GC progression. Here, we found that LINC00339 was overexpressed expressed in GC tissues and predicted poor outcome. By CCK8, colony formation and Transwell assays, we showed LINC00339 knockdown suppressed GC cell proliferation, migration, and invasion in vitro. Flow cytometry analysis (FACS) indicated that LINC00339 knockdown induced tumor cell apoptosis. Besides, we utilized the xenograft assay and found that LINC00339 depletion led to decreased tumor growth in vivo. Mechanistically, miR-377-3p was found to be inhibited by LINC00339. And LINC00339 suppressed miR-377-3p to upregulate DCP1A, which consequently promoted GC progression. In conclusion, LINC00339 promotes gastric cancer progression by elevating DCP1A expression via inhibiting miR-377-3p.     

Inhibited HDAC3 promotes microRNA-376c-3p to suppress malignant phenotypes of gastric cancer cells by reducing WNT2b

ObjectiveOur study aims to identify the impact of histone deacetylase 3 (HDAC3) and microRNA-376c-3p (miR-376c-3p) on gastric cancer (GC) by targeting wingless-type MMTV integration site family member 2b (WNT2b).MethodsLevels of miR-376c-3p, HDAC3 and WNT2b were assessed. GC cells were treated with altered HDAC3 or miR-376c-3p to evaluate their biological functions, and rescue experiment was performed to assess the effect of WNT2b on GC cells. The tumor growth in vivo was observed.ResultsHDAC3 and WNT2b were up-regulated while miR-376c-3p was reduced in GC tissues and cell lines. The inhibited HDAC3 or elevated miR-376c-3p could restrain malignant behaviors of GC cells in vitro, and also suppress the xenograft growth. WNT2b silencing reduced the effect of miR-376c-3p inhibition while WNT2b overexpression mitigated that of miR-376c-3p promotion on GC cell growth.ConclusionInhibiting HDAC3 promotes miR-376c-3p to suppress malignant phenotypes of GC cells via reducing WNT2b, thereby restricting GC development.     

Effects of long non-coding RNA LINC00667 on renal tubular epithelial cell proliferation,apoptosis and renal fibrosis via the miR-19b-3p/LINC00667/CTGF signaling pathway in chronic renal failure

The global prevalence of chronic renal failure (CRF) has significantly elevated with various reports indicating there to be a 10% worldwide rate. The functions of long non-coding RNAs (lncRNAs) and their deeper association with CRF at present remain poorly understood. Hence, the aim of the present study was to investigate the altered expressions of lncRNA LINC00667 in CRF and its associated effects on renal tubular epithelial cell proliferation, apoptosis and renal fibrosis through the microRNA-19b-3p (miR-19b-3p)/LINC00667/connective tissue growth factor (CTGF) signaling pathway. Initially, verification of the targeting relationship between LINC00667, CTGF and miR-19b-3p was performed, after which evidence was obtained indicating that miR-19b-3p could negatively regulate LINC00667 and CTGF. The expressions of CTGF in both the CRF and normal renal tissues were determined by immunohistochemistry means, with LINC00667 and CTGF determined to be highly expressed, while poor expression levels of miR-19b-3p were detected among the CRF tissues. The expressions of LINC00667, miR-19b-3p, fibrosis- and epithelial-mesenchymal transition (EMT)-related genes were also examined. The successfully established CRF rat models were treated with varying mimics, inhibitors, and siRNA. ELISA was applied to determine the renal function-related factors. Besides, the renal cell proliferation, migration and apoptosis were detected. In response to LINC00667 silencing, the renal tubular epithelial cells displayed increased proliferation and migration accompanied by reduced apoptosis based on upregulated miR-19b-3p, along with inhibited renal fibrosis and EMT detected. Taken together, the key findings of our study demonstrated that decreased lncRNA LINC00667 could promote renal tubular epithelial cell proliferation and ameliorate renal fibrosis in CRF via the miR-19b-3p/LINC00667/CTGF signaling pathway.     

LINC00152 promotes cell cycle progression in hepatocellular carcinoma via miR-193a/b-3p/CCND1 axis

Long intergenic non-coding RNA 00152 (LINC00152) is aberrantly expressed in various human malignancies and plays an important role in the pathogenesis. Here, we found that LINC00152 is upregulated in hepatocellular carcinoma (HCC) tissues as compared to adjacent non-neoplastic tissues; gain-and-loss-of-function analyses in vitro showed that LINC00152 facilitates HCC cell cycle progression through regulating the expression of CCND1. LINC00152 knockdown inhibits tumorigenesis in vivo. MS2-RIP analysis indicated that LINC00152 binds directly to miR-193a/b-3p, as confirmed by luciferase reporter assays. Furthermore, ectopic expression of LINC00152 partially halted the decrease in CCND1 expression and cell proliferation capacity induced by miR-193a/b-3p overexpression. Thus, LINC00152 acts as a competing endogenous RNA (ceRNA) by sponging miR-193a/b-3p to modulate its target gene, CCND1. Our findings establish a ceRNA mechanism regulating cell proliferation in HCC via the LINC00152/miR-193a/b-3p/CCND1 signalling axis, and identify LINC00152 as a potential therapeutic target for HCC.     

The Smad3-miR-29b/miR-29c axis mediates the protective effect of macrophage migration inhibitory factor against cardiac fibrosis

Although macrophage migration inhibitory factor (MIF) is known to have antioxidant property, the role of MIF in cardiac fibrosis has not been well understood. We found that MIF was markedly increased in angiotension II (Ang-II)-infused mouse myocardium. Myocardial function was impaired and cardiac fibrosis was aggravated in Mif-knockout (Mif-KO) mice. Functionally, overexpression of MIF and MIF protein could inhibit the expression of fibrosis-associated collagen (Col) 1a1, COL3A1 and α-SMA, and Smad3 activation in mouse cardiac fibroblasts (CFs). Consistently, MIF deficiency could exacerbate the expression of COL1A1, COL3A1 and α-SMA, and Smad3 activation in Ang-II-treated CFs. Interestingly, microRNA-29b-3p (miR-29b-3p) and microRNA-29c-3p (miR-29c-3p) were down-regulated in the myocardium of Ang-II-infused Mif-KO mice but upregulated in CFs with MIF overexpression or by treatment with MIF protein. MiR-29b-3p and miR-29c-3p could suppress the expression of COL1A1, COL3A1 and α-SMA in CFs through targeting the pro-fibrosis genes of transforming growth factor beta-2 (Tgfb2) and matrix metallopeptidase 2 (Mmp2). We further demonstrated that Mif inhibited reactive oxygen species (ROS) generation and Smad3 activation, and rescued the decrease of miR-29b-3p and miR-29c-3p in Ang-II-treated CFs. Smad3 inhibitors, SIS3 and Naringenin, and Smad3 siRNA could reverse the decrease of miR-29b-3p and miR-29c-3p in Ang-II-treated CFs. Taken together, our data demonstrated that the Smad3-miR-29b/miR-29c axis mediates the inhibitory effect of macrophage migration inhibitory factor on cardiac fibrosis.     

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.     

LINC01579 promotes cell proliferation by acting as a ceRNA of miR-139-5p to upregulate EIF4G2 expression in glioblastoma

Glioblastoma (GBM), a malignant and lethal tumor, remains a big threat to human health and life. Increasing explorations have confirmed that long noncoding RNAs are involved in the tumorigenesis and development of multiple cancers. Nevertheless, the regulatory mechanism of (long intergenic nonprotein coding RNA 1579 LINC01579) in GBM remains to be investigated. In this study, the expression of LINC01579 was upregulated in GBM cells and LINC01579 knockdown inhibited cell proliferation as well as promoted cell apoptosis. Additionally, LINC01579 acted as a sponge for miR-139-5p in GBM and eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) was found to be a downstream target of miR-139-5p. Furthermore, the positive correlation of LINC01579 and EIF4G2 as well as the converse correlation between miR-139-5p and LINC01579 (or EIF4G2) were revealed by the experiments. Based on rescue assays, EIF4G2 overexpression or miR-139-5p inhibitor partially recovered the function of LINC01579 knockdown on cell proliferation and apoptosis. In summary, the results of this study verified that LINC01579 modulated cell proliferation and cell apoptosis in GBM by competitively binding with miR-139-5p to regulate EIF4G2, which provided a new clue to figure out potential therapy for patients suffered from GBM.     

LncRNA HOTTIP inhibits cell pyroptosis by targeting miR-148a-3p/AKT2 axis in ovarian cancer

Long noncoding RNA HOTTIP is a crucial regulator in multiple types of cancer, including ovarian cancer (OC). However, the biological roles and underlying mechanisms of HOTTIP in OC have rarely been studied. Hence, this study aimed to investigate the functional correlation between HOTTIP and pyroptosis in OC progression. The expression of HOTTIP in OC tissues and cell lines was characterized by quantitative real-time PCR. Cell proliferation was evaluated using Cell Counting Kit-8 and clone formation assays. Western blot was performed to quantify protein levels. A dual-luciferase reporter assay was used to analyze the molecular interaction among HOTTIP, miR-148a-3p, and AKT2. The expression of HOTTIP was significantly upregulated in OC tissue samples and cell lines. The silencing of HOTTIP led to the inhibition of cell proliferation and NLRP1 inflammasome-mediated pyroptosis. In addition, HOTTIP increased AKT2 expression by negatively regulating miR-148a-3p and then inhibited ASK1/JNK signaling. Further rescue experiments revealed that downregulation of miR-148a-3p and overexpression of AKT2 obviously diminished the effects of HOTTIP downregulation in OC cells. Thus, our study elucidated a novel pyroptosis-related mechanism by which HOTTIP participated in OC progression, which might provide a theoretical reference for clinical treatment.     

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.     

Silencing LINC00504 inhibits cell proliferation,invasion as well as migration and promotes cell apoptosis in lung cancer cells via upregulating miR-876-3p

LINC00504 acts as an oncogene and associates with unfavorable prognosis in patients with lung cancer. Silencing LINC00504 may be a promising strategy for treatment of lung cancer and its effects were firstly investigated in lung cancer cells this study. The gene expression level of miR-876-3p as well as LINC00504 were measured via PCR assay. The cell proliferation was investigated through Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Flow cytometry was applied for detection of cell apoptosis. Wound healing and transwell assay were performed for measurement of cell migration and invasion respectively. The apoptosis related protein expressions were measured by western blot. Luciferase report assay was conducted for verification the target gene. LINC00504 was higher expressed in five types of lung cancer cells studied herein when compared with the control normal cells. LINC00504 knockdown exerted inhibitory effects on cell apoptosis, cell migration as well as cell invasion and promoted cell apoptosis. All the effects mentioned above were counteracted by miR-876-3p inhibitor. Silencing LINC00504 possessed anti-proliferation, repression of cell invasion as well as migration and pro-apoptosis effects via targeting up-regulation of miR-876-3p in lung cancer cells, proving the new therapeutic targets and highlighting the potential application in future diagnosis and treatment in lung cancer.     

LINC00707 promotes hepatocellular carcinoma progression through activating ERK/JNK/AKT pathway signaling pathway

Increasing evidence has demonstrated that abnormal expression of lncRNA is correlated with various malignant tumors, including hepatocellular carcinoma (HCC). Our current study was aimed to investigate the role of LINC00707 in HCC development. We observed that LINC00707 was upregulated in HCC cell lines compared with normal liver cell lines. Then, Hep3B cells and SNU449 cells were infected with LV-shLINC00707 and LV-LINC00707. LINC00707 silencing could greatly repress the proliferation and colony formation of HCC cells in vitro. On the contrary, overexpression of LINC00707 induced HCC cell proliferation and colony formation. In addition, HCC cell apoptosis was significantly enhanced and HCC cell cycle was blocked in G1 phase by LV-shLINC00707. Hep3B cells and SNU449 cell invasion capacity was restrained by the knockdown of LINC00707, whereas upregulation of LINC00707 exhibited an opposite phenomenon. Accumulating evidence has reported that ERK/JNK/AKT signaling is involved in multiple cancers, including HCC. Here, in our study, we identified that ERK/JNK/AKT signaling was dramatically restrained by silencing of LINC00707 while activated by LV-LINC00707 in HCC cells. Subsequently, an in vivo experiment was conducted, and it demonstrated that LINC00707 could modulate HCC development through activating ERK/JNK/AKT signaling. Taking the above results together, it was implied in our study that LINC00707 contributed to HCC progression through modulating the ERK/JNK/AKT pathway.     

LINC00461 promotes cell migration and invasion in breast cancer through miR-30a-5p/integrin β3 axis

Mounting evidence has demonstrated that long noncoding RNAs (lncRNAs) are dysregulated and implicated in the occurrence and development of a wide range of human malignancies. LINC00461, a novel cancer-related lncRNA, has been reported to be highly expressed and serve as oncogene in glioma; however, its biological role in breast cancer (BC) remains obscure. This study aimed to explore the role of LINC00461 in BC and elucidate the potential molecular mechanisms involved. In the current study, LINC00461 was found to be significantly upregulated in both BC tissues and cell lines. Besides, we found that high LINC00461 expression was associated with TNM stage and differentiation. Furthermore, functional studies demonstrated that LINC00461 expedited BC cell migration and invasion. Notably, LINC00461 was observed to enhance the expression of vimentin and zinc-finger E-box binding homeobox factor 1, suppress the expression of E-cadherin, and promote the activation of extracellular signal-regulated kinase and AKT signaling pathways. Mechanical investigations revealed that LINC00461 positively modulated integrin β3 (ITGB3) expression as miR-30a-5p sponge in BC cells. Taken together, LINC00461 exerts an oncogenic role in BC through miR-30a-5p/ITGB3 axis. Our data indicate that LINC00461 may be used to be a novel candidate therapeutic target and a valuable diagnostic biomarker for BC.