Knocking-down long non-coding RNA LINC01094 prohibits chondrocyte apoptosis via regulating microRNA-577/metal-regulatory transcription factor 1 axis.

PURPOSE: The abnormal function and survival of chondrocytes result in articular cartilage failure, which may accelerate the onset and development of osteoarthritis (OA). This study is aimed to investigate the role of LINC01094 in chondrocyte apoptosis. METHODS: The viability and apoptosis of lipopolysaccharide (LPS)-induced chondrocytes were evaluated through CCK-8 assay and flow cytometry analysis, respectively. The expression levels of LINC01094, miR-577 and MTF1 were detected by qRT-PCR. Dual luciferase reporter tests were implemented for the verification of targeted relationships among them. Western blotting was employed to measure the levels of pro-apoptotic proteins (Caspase3 and Caspase9). RESULTS: The viability of LPS-induced chondrocytes was overtly promoted by loss of LINC01094 or miR-577 upregulation, but could be repressed via MTF1 overexpression. The opposite results were observed in apoptosis rate and the levels of Caspase3 and Caspase9. LINC01094 directly bound to miR-577, while MTF1 was verified to be modulated by miR-577. Both LINC01094 and MTF1 were at high levels, whereas miR-577 was at low level in OA synovial fluid and LPS-induced chondrocytes. Furthermore, the highly expressed miR-577 abolished the influences of MTF1 overexpression on LPS-induced chondrocytes. CONCLUSIONS: Silencing of LINC01094 represses the apoptosis of chondrocytes through upregulating miR-577 expression and downregulating MTF1 levels, providing a preliminary insight for the treatment of OA in the future.

LncRNA LINC01094 Promotes Cells Proliferation and Metastasis through the PTEN/AKT Pathway by Targeting AZGP1 in Gastric Cancer.

Long noncoding RNAs (lncRNAs) were recently reported to play an essential role in multiple cancer types. Herein, through next-generation sequencing, we screened metastasis-driving molecules by using tissues from early-stage gastric cancer (GC) patients with lymph node metastasis, and we identified a lncRNA LINC01094, which was associated with the metastasis of GC. According to the clinical data from the TCGA, GSE15459, and GSE62254 cohorts, the high expression of LINC01094 was associated with an unfavorable prognosis. Moreover, 106 clinical GC and paired normal samples were collected, and the qRT-PCR results showed that the high expression of LINC01094 was associated with high T and N stages and a poor prognosis. We found that LINC01094 promotes the proliferation and metastasis of GC in vitro and in vivo. AZGP1 was found as the protein-binding partner of LINC01094 by using RNA pulldown and RNA-binding protein immunoprecipitation (RIP) assays. LINC01094 antagonizes the function of AZGP1, downregulates the expression of PTEN, and further upregulates the AKT pathway. Collectively, our results suggested that LINC01094 might predict the prognosis of GC patients and become the therapy target for GC.

Upregulated long intergenic non-protein coding RNA 1094 (LINC01094) is linked to poor prognosis and alteration of cell function in colorectal cancer.

Colorectal cancer (CRC) showed high cancer-related mortality in recent years partly due to the absence of an effective prognostic predictor. This research intended to evaluate the prognostic value and potential role of long intergenic non-protein coding RNA 1094 (LINC01094) in CRC. In this work, we evaluated the LINC01094 level in 122 CRC patients' tissues and in human CRC cell lines. We explored the ability of LINC01094 in overall survival and progression-free survival estimate. The effect of LINC01094 dysregulation on the CRC cells was investigated. LINC01094 is highly expressed in CRC tissues and cells than normal ones. This high expression was correlated with absent vascular invasion, positive lymph node metastasis, and advanced TNM stage. With the result of Kaplan-Meier analysis and multivariate Cox's proportional hazard analysis, LINC01094 was an effective biomarker for CRC overall survival. Downregulation of LINC01094 impeded the malignant biological behavior (proliferation, invasion, and migration) of CRC cells, while overexpression of LINC01094 boosted that maybe by sponging miR-1266-5p. LINC01094 might function as an oncogene in CRC and allowed the discovery of a new biomarker for prognosis and therapy of CRC.

LncRNA LINC01094 contributes to glioma progression by modulating miR-224-5p/CHSY1 axis.

Glioma serves as the most common malignancy influencing modern people and is associated with severe morbidity and high mortality. Long non-coding RNAs (lncRNAs) as crucial regulators participate in multiple cancer progression. However, the role of lncRNA LINC01094 in the development of glioma remains unclear. Here, we aimed to explore the effect of lncRNA LINC01094 on the glioma progression and the underlying mechanism. Significantly, we revealed that the expression levels of LINC01094 were elevated in the glioma patient tissues compared to adjacent normal tissues. The LINC01094 expression was enhanced in the glioma cell lines. The depletion of LINC01094 inhibited cell viability and colony formation in the glioma cells. Meanwhile, the migration and invasion of glioma cells were impaired by the depletion of LINC01094. Mechanically, we identified that LINC01094 was able to sponge the miR-224-5p in the glioma cells and miR-224-5p inhibitor could reverse the effect of LINC01094 on glioma progression. In addition, miR-224-5p targeted CHSY1 and LINC01094 up-regulated CHSY1 by targeting miR-224-5p in the glioma cells. LINC01094 promoted glioma progression by the positive regulation of CHSY1. Moreover, tumorigenicity analysis showed that LINC01094 enhanced tumor growth of glioma in vivo. Thus, we conclude that lncRNA LINC01094 promotes glioma progression by modulating miR-224-5p/CHSY1 axis. Our finding provides new insights into the mechanism by which lncRNA LINC01094 contributes to the development of glioma, improving the understanding of lncRNA LINC01094 and glioma. LncRNA LINC01094, miR-224-5p, and CHSY1 may serve as potential targets for glioma.

LINC01094 promotes pancreatic cancer progression by sponging miR-577 to regulate LIN28B expression and the PI3K/AKT pathway.

The leading cause of death in pancreatic cancer (PC) patients is the progression of cancer metastasis. Recently, long non-coding RNAs (lncRNAs) have been shown to play an important role in regulating cancer cell proliferation and metastasis; however, its molecular basis in PC remains to be explored. In this study, we observed that LINC01094 was markedly overexpressed in PC tissues and was associated with poor patient prognosis. Downregulation of LINC01094 decreased the proliferation and metastasis of PC cells and inhibited tumorigenesis and metastasis in mouse xenografts. Mechanically, LINC01094 acted as an endogenous miR-577 sponge to increase the expression of its target gene, the RNA-binding protein lin-28 homolog B (LIN28B), by decoying the miR-577, thereby activating the PI3K/AKT pathway. Our findings suggest that LINC01094 plays critical roles in proliferation and metastasis of PC, implying that LINC01094 can be regarded as a new biomarker or therapeutic target for the treatment of PC.

Long intergenic non-protein coding RNA 1094 (LINC01094) promotes the progression of breast cancer (BC) by regulating the microRNA-340-5p (miR-340-5p)/E2F transcription factor 3 (E2F3) axis.

The present study was targeted at investigating the effects of long intergenic non-protein coding RNA 1094 on breast cancer (BC) cell proliferation, apoptosis, and cell cycle and its related mechanism. In this study, Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to detect the expressions of LINC01094, microRNA (miRNA, miR)-340-5p, and E2F transcription factor 3 (E2F3) in BC tissues and cells. With transfection, LINC01094 and miR-340-5p expressions were selectively up-regulated or down-regulated in BC cell lines, and then cell proliferation, cell cycle, and apoptosis were examined by cell counting kit-8 (CCK-8), 5-bromo-2'-deoxyuridine (BrdU), and flow cytometry assays. Bioinformatics was utilized to predict the targeted relationships between miR-340-5p and LINC01094, as well as miR-340-5p and E2F3 mRNA 3'-untranslated region (3'UTR), and RNA immunoprecipitation (RIP) assay and dual-luciferase reporter gene assay were employed to validate them. It was revealed that, LINC01094 expression was enhanced in BC cells and tissues, and LINC01094 overexpression promoted BC cell proliferation, accelerated cell cycle progression, and inhibited apoptosis while knocking down LINC01094 worked oppositely. LINC01094 directly targeted miR-340-5p and negatively regulated its expression in BC cells. Besides, E2F3 was substantiated to be the target gene of miR-340-5p, and E2F3 expression could be indirectly and positively modulated by LINC01094. All in all, LINC01094 promotes BC cell proliferation and cell cycle progression and inhibits apoptosis via modulating miR-340-5p/E2F3 molecular axis.

Long Non-coding RNA LINC01094 Promotes the Development of Clear Cell Renal Cell Carcinoma by Upregulating SLC2A3 via MicroRNA-184.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC. Compelling evidence has highlighted the crucial role of long non-coding RNA (lncRNA) in ccRCC. Our current study aims to explore the regulatory mechanism of LINC01094 in the development of ccRCC. Dual-luciferase reporter experiment verified the targeting relationship among miR-184, LINC01094, and SLC2A3. Furthermore, the interaction between LINC01094 and miR-184 was confirmed by RNA immunoprecipitation (RIP) and RNA pull-down. Biological behaviors of ccRCC cells were investigated through cell counting kit-8 (CCK8), scratch test, Transwell, and flow cytometry. The effect of SLC2A3 on the tumorigenicity of nude mice was evaluated in vivo. In ccRCC cells and clinical tissues, LINC01094 and SLC2A3 were highly expressed while miR-184 was lowly expressed. Besides, miR-184 was verified to be a direct target of LINC01094. Silencing LINC01094, up-regulating miR-184, or reducing SLC2A3 inhibited the growth, migration, and invasion of ccRCC cells. Tumor growth was suppressed by silenced LINC01215 via reducing the expression of SLC2A3 via miR-184. Taken together, silencing LINC01094 inhibited SLC2A3 expression by up-regulating miR-184, thereby inhibiting the development of ccRCC.

Linc01094 Accelerates the Growth and Metastatic-Related Traits of Glioblastoma by Sponging miR-126-5p.

BACKGROUND: Long intergenic non-coding RNAs (lincRNAs) are associated with the progression of glioblastoma (GBM). However, how linc01094 contributes to the growth and metastatic phenotypes of GBM remains not fully studied. METHODS: The expression levels of linc01094 and miR-126-5p in GBM tissues and cell lines were analyzed using qRT-PCR. Loss-of-function experiments were performed to detect the biological activity of linc01094 in GBM. Glioblastoma tumor model was constructed to explore the impact of linc01094 on GBM cell growth in vivo. Linc01094-sponged miR-126-5p was certified by luciferase reporter assay and RNA immunoprecipitation (RIP). The protein expression of miRNA target gene, dynactin subunit 4 (DCTN4) was detected using Western blotting assay. RESULTS: Herein, we observed that the level of linc01094 was higher in GBM tissues. Silencing of linc01094 restrained the growth and invasive abilities of GBM cell. Moreover, linc01094 level was negatively associated with miR-126-5p level in GBM and linc01094 acted as a "sponge" for miR-126-5p. Reintroduction of linc01094 reversed the tumor-inhibiting effects of miR-126-5p in GBM. CONCLUSION: Altogether, linc01094 promoted the tumorigenesis and metastatic phenotypes of GBM cell by modulating of miR-1126-5p/DCTN4 signaling axis.

LINC01094/miR-577 axis regulates the progression of ovarian cancer.

BACKGROUND: Long intergenic non-coding RNA 01094 (LINC01094) is probably a novel regulator in cancer biology. This study aimed to probe into the function and mechanism of LINC01094 in ovarian cancer (OC). METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was utilized to measure LINC01094 and miR-577 expressions in OC tissues and cell lines. Western blot was used to examine the expressions of epithelial-mesenchymal transition (EMT)-related proteins, ß-catenin, c-Myc and cyclin D1. Cell counting kit-8 (CCK-8) and Transwell assays were used to detect the proliferation, migration and invasion of SKOV3 and 3AO cells, respectively. Eventually, dual-luciferase reporter gene assay was employed to detect the regulatory relationship between miR-577 and LINC01094. RESULTS: LINC01094 expression was elevated in OC tissues and cell lines. High LINC01094 expression was associated with higher FIGO stage, lymph node metastasis and the shorter overall survival rate in patients with OC. Meanwhile, LINC01094 knockdown inhibited OC cell proliferation, migration, invasion and EMT. In addition, miR-577 was demonstrated to be a direct downstream target of LINC01094 in OC and inhibition of miR-577 reversed the biological effects of LINC01094 knockdown on OC cells. Additionally, LINC01094 / miR-577 axis regulated the expressions of ß-catenin, c-Myc and cyclin D1 in OC cells. CONCLUSION: LINC01094 promotes the proliferation, migration, invasion and EMT of OC cells by adsorbing miR-577.

LINC01094 Down-Regulates miR-330-3p and Enhances the Expression of MSI1 to Promote the Progression of Glioma.

BACKGROUND: This study aims at probing into the expression, function, and mechanism of LINC01094 and miR-330-3p in glioma. MATERIALS AND METHODS: qRT-PCR was employed to examine LINC01094 and miR-330-3p expressions in gliomas. After gain-of-function and loss-of-function models were constructed, CCK-8 and Transwell assays were used to detect the proliferation, migration and invasion of LN229 and U251 cells, respectively. Additionally, dual luciferase reporter gene assay was utilized to verify the binding site between m4iR-330-3p and LINC01094, miR-330-3p, and the 3'UTR of musashi RNA binding protein 1 (MSI1). Then, RNA pull-down, RIP, qRT-PCR and Western blot were employed to detect the regulatory relationships among LINC01094, miR-330-3p, and MSI1. RESULTS: The expression of LINC01094 was elevated in glioma tissues and cell lines, and the high expression of LINC01094 was associated with high grade of glioma. In contrast, miR-330-3p was lowly expressed in glioma tissue. Overexpression of LINC01094 or down-regulation of miR-330-3p promoted the proliferation, migration, and invasion of glioma cells, while LINC01094 knockdown or miR-330-3p up-regulation impeded these processes. miR-330-3p was identified as a target miRNA of LINC01094, and it could be negatively regulated by LINC01094. In addition, miR-330-3p antagonized the function of LINC01094 by negatively regulating MSI1. CONCLUSION: LINC01094 promotes the proliferation, migration, and invasion of glioma cells by adsorbing miR-330-3p and up-regulating the expression of MSI1.

LINC01094 triggers radio-resistance in clear cell renal cell carcinoma via miR-577/CHEK2/FOXM1 axis.

BACKGROUND: Radioresistance is an obstacle to limit efficacy of radiotherapy. Meanwhile, long non-coding RNAs (lncRNAs) have been reported to affect radioresistance. Here, we aimed to investigate lncRNAs involving radioresistance development of clear cell renal cell carcinoma (ccRCC), the most frequent type of renal cell carcinoma (RCC). METHODS: The mRNA and protein expressions of genes were measured via qRT-PCR and western blot. The relationships among genes were verified by RIP and luciferase reporter assay. The radioresistance of ccRCC cells was evaluated through clonogenic survival assay, MTT assay and TUNEL assay. RESULTS: LINC01094 was over-expressed in ccRCC cell lines. LINC01094 expression was increased along with the radiation exposure time and the final stable level was 8 times of the initial level. Knockdown of LINC01094 resulted in enhanced radiosensitivity of ccRCC cells. Mechanically, LINC01094 was a ceRNA of CHEK2 by sponging miR-577. Also, the enhancement of LINC01094 on ccRCC radioresistance was mediated by CHEK2-stabilized FOXM1 protein. CONCLUSION: LINC01094 facilitates ccRCC radioresistance by targeting miR-577/CHEK2/FOXM1 axis, blazing a new trail for overcoming radioresistance in ccRCC.

FOXM1-Activated LINC01094 Promotes Clear Cell Renal Cell Carcinoma Development via MicroRNA 224-5p/CHSY1.

Clear cell renal cell carcinoma (ccRCC) is regarded as the most aggressive subtype of RCC, with high rates of metastasis and recurrence. An extensive body of studies had proved long noncoding RNAs (lncRNAs) play pivotal parts in the development and evolution of diverse malignant tumors. However, the potential of LINC01094 in ccRCC tumorigenesis is still unexplored. In the present research, with the aid of the TCGA database, we found that LINC01094 was highly expressed in ccRCC tissues. Upregulation of LINC01094 was also confirmed in ccRCC cell lines, and functional experiments delineated that LINC01094 knockdown led to inhibition on ccRCC cell growth and metastasis. Moreover, LINC01094 was activated by FOXM1 at the transcriptional level. Further assay demonstrated that LINC01094 worked as a sponge of microRNA 224-5p (miR-224-5p) and CHSY1 was a miR-224-5p-targeted mRNA. Further, we verified that LINC01094 acted as a competing endogenous RNA in ccRCC to regulate CHSY1 expression via competitively bind to miR-224-5p. Lastly, our results expounded that LINC01094 exerted its tumor-promoting performance in ccRCC development through miR-224-5p/CHSY1 regulatory axis, which shed light on the molecular mechanism underlying LINC01094 in ccRCC and opened a new prospective for the treatment of ccRCC.