Long noncoding RNA-mediated activation of PROTOR1/PRR5-AKT signaling shunt downstream of PI3K in triple-negative breast cancer.

The phosphoinositide 3-kinase (PI3K) pathway represents the most hyperactivated oncogenic pathway in triple-negative breast cancer (TNBC), a highly aggressive tumor subtype encompassing ∼15% of breast cancers and which possesses no targeted therapeutics. Despite critical contributions of its signaling arms to disease pathogenesis, PI3K pathway inhibitors have not achieved expected clinical responses in TNBC, owing largely to a still-incomplete understanding of the compensatory cascades that operate downstream of PI3K. Here, we investigated the contributions of long noncoding RNAs (lncRNAs) to PI3K activities in clinical and experimental TNBC and discovered a prominent role for LINC01133 as a PI3K-AKT signaling effector. We found that LINC01133 exerted protumorigenic roles in TNBC and that it governed a previously undescribed mTOR Complex 2 (mTORC2)-dependent pathway that activated AKT in a PI3K-independent manner. Mechanistically, LINC01133 induced the expression of the mTORC2 component PROTOR1/PRR5 by competitively coupling away its negative messenger RNA (mRNA) regulator, the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1). PROTOR1/PRR5 in turn was sufficient and necessary for LINC01133-triggered functions, casting previously unappreciated roles for this Rictor-binding protein in cellular signaling and growth. Notably, LINC01133 antagonism undermined cellular growth, and we show that the LINC01133-PROTOR1/PRR5 pathway was tightly associated with TNBC poor patient survival. Altogether, our findings uncovered a lncRNA-driven signaling shunt that acts as a critical determinant of malignancy downstream of the PI3K pathway and as a potential RNA therapeutic target in clinical TNBC management.

Silencing long noncoding RNA LINC01133 suppresses pancreatic cancer through regulation of microRNA-1299-dependent IGF2BP3.

The deregulation of long noncoding RNAs (lncRNAs) holds great potential in the treatment of multiple cancers, including pancreatic cancer (PC). However, the specific molecular mechanisms by which LINC01133 contributes to pancreatic cancer remain unknown. Subsequent to bioinformatics analysis, we predicted and analyzed differentially expressed lncRNAs, microRNAs, and genes in pancreatic cancer. We determined the expression patterns of LINC01133, miR-1299, and insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in pancreatic cancer cells, and validated their interactions through luciferase reporter and RNA immunoprecipitation assays. We implemented loss-of-function and gain-of-function experiments for LINC01133, miR-1299, and IGF2BP3 to assay their potential effects on pancreatic cancer cell functions. We observed high expression of LINC01133 and IGF2BP3, but low expression of miR-1299, in pancreatic cancer cells. Furthermore, we found that LINC01133 enhances IGF2BP3 through binding with miR-1299. Silencing LINC01133 or IGF2BP3 and/or overexpressing miR-1299 limited pancreatic cancer cell proliferation, invasion, epithelial-mesenchymal transition, and suppressed tumorigenic abilities in mice lacking T cells (nude mice). Overall, our findings identified that silencing LINC01133 downregulates IGF2BP3 by upregulating miR-1299 expression, ultimately leading to the prevention of pancreatic cancer.

A review on the role of LINC01133 in cancers.

Long Intergenic Non-Protein Coding RNA 1133 (LINC01133) is a long non-coding RNA (lncRNA) which interacts with miR-106a-3p, miR-576-5p, miR-495-3p, miR-205, miR-199a-5p, miR-4784, miR-30a-5p, miR-199a, miR-30b-5p, miR-216a -5p and miR-422a, thus increasing expression of mRNA targets of these miRNAs. LINC01133 can affect cancer metastasis through regulation of epithelial-mesenchymal transition program. Dysregulation of this lncRNA has been repeatedly detected in the process of tumorigenesis. In this review, we summarize the results of various studies that reported dysregulation of LINC01133 in different samples and described the role of this lncRNA as a marker for these disorders.

Expression profiles and functional prediction of long non-coding RNAs LINC01133, ZEB1-AS1 and ABHD11-AS1 in the luminal subtype of breast cancer.

BACKGROUND: Luminal breast cancer (BC) is the most frequent subtype accounting for more than 70% of BC. LncRNAs, a class of non-coding RNAs with more than 200 nucleotides, are involved in a variety of cellular processes and biological functions. Abberant expression is related to the development of various cancers, such as breast cancer. LINC01133, ZEB1-AS1, and ABHD11-AS1 were reported to be dysregulated in different cancers. However, their expression level in luminal BC remains poorly known. The aim of the present study was to evaluate the potential roles of these lncRNAs in BC, especially in luminal subtypes. METHODS: A comprehensive analysis was performed using the Lnc2Cancer database to identify novel cancer-associated lncRNA candidates. After conducting a literature review, three novel lncRNAs named LINC01133, ZEB1-AS1, and ABHD11-AS1 were chosen as target genes of the present study. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of the mentioned lncRNAs in both luminal BC tissues and cell lines. Then, the correlation of the three mentioned lncRNAs expression with clinicopathological characteristics of the patients was studied. Moreover, several datasets were used to discover the potential roles and functions of LINC01133, ZEB1-AS1 and ABHD11-AS1 in luminal subtype of BC. RESULTS: According to the qRT-PCR assay, the expression levels of LINC01133 and ZEB1-AS1 were decreased in luminal BC tissues and cell lines. On the other hand, ABHD11-AS1 was upregulated in the above-mentioned samples. The expression levels of LINC01133, ZEB1-AS1, and ABHD11-AS1 were not associated with any of the clinical features. Also, the results obtained from the bioinformatics analyses were consistent with qRT-PCR data. Functional annotation of the co-expressed genes with the target lncRNAs, protein-protein interactions and significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways across luminal BC were also obtained using bioinformatics analysis. CONCLUSIONS: Taken together, our findings disclosed the dysregulation of LINC01133, ZEB1-AS1, and ABHD11-AS1 in luminal BC. It was revealed that LINC01133 and ZEB1-AS1 expression was significantly downregulated in luminal BC tissues and cell lines, while ABHD11-AS1 was upregulated considerably in the mentioned tissues and cell lines. Also, bioinformatics and systems biology analyses have helped to identify the possible role of these lncRNAs in luminal BC. However, further analysis is needed to confirm the current findings.

Exosomes-mediated transfer of long noncoding RNA LINC01133 represses bladder cancer progression via regulating the Wnt signaling pathway.

Bladder cancer (BC), as one of the most common malignant cancers of the urinary system, has a high incidence and mortality rates. Recently, increasing studies have indicated that exosomes can mediate cellular communication in assorted cancers, including BC. Long noncoding RNAs (lncRNAs) have also been confirmed to take part in the regulation of many cancers. Long intergenic non-protein coding RNA 1133 (LINC01133) is an lncRNA and its roles in several cancers have been revealed. However, the functions of exosomes and LINC01133 in BC are still not elucidated. In our research, functional assays were conducted to evaluate the function of LINC01133, as well as the influence of exosomes and LINC01133 on BC cells. Western blot assay, immunofluorescence assay, electron microscope, and nanoparticle tracking analysis were applied for detecting the characteristics of exosomes. Bioinformatics tools and quantitative reverse-transcription polymerase chain reaction were performed to test the expression of LINC01133 in BC cells and exosomes of the immortalized human uroepithelial cell line (SV-HUC-1). Luciferase reporter assay was performed to measure the activity of the Wnt pathway. We discovered that LINC01133 expression was high in exosomes of SV-HUC-1 and low in that of BC cells. Additionally, exosomes restrained cell viability, proliferation, migration, and invasion. Similarly, LINC01133 exerted the same function on BC cells. In addition, the Wnt signaling pathway could be inactivated by LINC01133. Finally, in vivo experiments demonstrated that cell growth could be suppressed by overexpressed LINC01133. In short, exosomes-mediated transfer of lncRNA LINC01133 repressed BC progression via regulating the Wnt signaling pathway.

LINC01133 contribute to epithelial ovarian cancer metastasis by regulating miR-495-3p/TPD52 axis.

Currently, there is increasing evidence that long noncoding RNAs (lncRNAs) initiate and promote the progression of epithelial ovarian cancer (EOC). In this study, we revealed the roles and the potential mechanisms of long intergenic non-protein coding RNA 1133 (LINC01133) in EOC, which remains not well understood. We found that LINC01133 was upregulated in EOC tissues and cell lines. Besides, it was associated with the clinicopathological feature of metastasis. Functional experiments demonstrated that LINC01133 could facilitate cancer cell migration and invasion in vitro and tumor metastasis in vivo. Further molecular mechanisms studies indicated that LINC01133 and miR-495-3p reciprocally repressed expression of each other. We also realized that LINC01133 shared the same binding sites for miR-495-3p with tumor protein D52 (TPD52). We confirmed that TPD52 functioned as a direct target of miR-495-3p and mediated the enhancing effect of LINC01133 on cancer metastasis. Generally, our study showed that LINC01133 interacted with miR-495-3p to promote metastasis in EOC by regulating TPD52. LINC01133 also provided a potential therapeutic perspective for future clinical treatment.

LINC01133 inhibits breast cancer invasion and metastasis by negatively regulating SOX4 expression through EZH2.

Mounting evidence highlights long non-coding RNAs (lncRNAs) as crucial regulators in multiple types of biological processes and contributing to tumourigenesis. LINC01133, located in chromosome 1q23.2, was a recently identified novel lncRNA with a length of 1154nt. It was involved in the development of colorectal cancer and non-small cell lung cancer. However, its clinical relevance, biological functions and potential molecular mechanism in breast cancer are still unclear. In this study, we found that the LINC01133 expression was significantly down-regulated in breast cancer samples and was associated with progression and poor prognosis of breast cancer. Further experiments demonstrated that overexpression of LINC01133 inhibited invasion and metastasis in breast cancer both in vitro and in vivo. Mechanistic investigations revealed that LINC01133 repressed SOX4 expression by recruiting EZH2 to SOX4 promoter. Moreover, rescue experiments further confirmed that LINC01133 functional acted as an anti-oncogene, at least partly, via repressing SOX4 in breast cancer. Taken together, these findings imply that LINC01133 could serve as a novel prognostic biomarker and potential therapeutic target for breast cancer.

LINC01133 aggravates the progression of hepatocellular carcinoma by activating the PI3K/AKT pathway.

LncRNAs exhibit crucial roles in various pathological diseases, including hepatocellular carcinoma (HCC). Therefore, it is significant to recognize the dysregulated lncRNAs in HCC progression. Recently, LINC01133 has been identified in several tumors. However, the biological role of LINC01133 in HCC remains poorly understood. Currently, we focused on the function of LINC01133 in HCC development. We observed that LINC01133 was significantly increased in HCC cells including HepG2, Hep3B, MHCC-97L, SK-Hep-1, and MHCC-97H cells compared with the normal human liver cell line HL-7702. In addition, PI3K/AKT signaling was highly activated in HCC cells. Knockdown of LINC01133 was able to inhibit HCC cell proliferation, cell colony formation, cell apoptosis, and blocked cell cycle arrest in the G1 phase. For another, downregulation of LINC01133 repressed HCC cell migration and invasion. Subsequently, the PI3K/AKT signaling pathway was strongly suppressed by silence of LINC01133 in Hep3B and HepG2 cells. Then, in vivo tumor xenografts models were established using Hep3B cells to explore the function of LINC01133 in HCC progression. Consistently, our study indicated that knockdown of LINC01133 dramatically repressed HCC tumor progression through targeting the PI3K/AKT pathway in vivo. Taken these together, we revealed that LINC01133 contributed to HCC progression by activating the PI3K/AKT pathway.

LINC01133 as ceRNA inhibits gastric cancer progression by sponging miR-106a-3p to regulate APC expression and the Wnt/ß-catenin pathway.

BACKGROUND: Gastric cancer (GC) is a common malignancy and frequent cause of cancer-related death. Long non-coding RNAs (lncRNAs) have emerged as important regulators and tissue-specific biomarkers of multiple cancers, including GC. Recent evidence has indicated that the novel lncRNA LINC01133 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in GC remain largely unknown. METHODS: LINC01133 expression was detected in 200 GC and matched non-cancerous tissues by quantitative reverse transcription PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of LINC01133 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, quantitative PCR arrays, TOPFlash/FOPFlash reporter assay, luciferase assay, and rescue experiments. RESULTS: LINC01133 was downregulated in GC tissues and cell lines, and its low expression positively correlated with GC progression and metastasis. Functionally, LINC01133 depletion promoted cell proliferation, migration, and the epithelial-mesenchymal transition (EMT) in GC cells, whereas LINC01133 overexpression resulted in the opposite effects both in vitro and in vivo. Bioinformatics analysis and luciferase assays revealed that miR-106a-3p was a direct target of LINC01133, which functioned as a ceRNA in regulating GC metastasis. Mechanistic analysis demonstrated that miR-106a-3p specifically targeted the adenomatous polyposis coli (APC) gene, and LINC01133/miR-106a-3p suppressed the EMT and metastasis by inactivating the Wnt/ß-catenin pathway in an APC-dependent manner. CONCLUSIONS: Our findings suggest that reduced expression of LINC01133 is associated with aggressive tumor phenotypes and poor patient outcomes in GC. LINC01133 inhibits GC progression and metastasis by acting as a ceRNA for miR-106a-3p to regulate APC expression and the Wnt/ß-catenin pathway, suggesting that LINC01133 may serve as a potential prognostic biomarker and anti-metastatic therapeutic target for GC.

Predictive Value of LINC01133 for Unfavorable Prognosis was Impacted by Alcohol in Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIMS: Considerable evidence indicates that long noncoding RNAs (lncRNAs) exert importantly regulatory functions during human cancer initiation and progression and are promising biotargets in the flight against cancer. METHODS: In this study, we evaluated the role of the lncRNA LINC01133 in esophageal squamous cell carcinoma (ESCC). LINC01133 expression in ESCC was examined by quantitative real-time PCR. The correlations between LINC01133 expression and clinicopathological variables and survival were examined by the χ2 test, Kaplan-Meier method, log-rank test, and univariate Cox regression analysis. RESULTS: LINC01133 expression levels were frequently lower in ESCC tissues and cell lines than in paired normal tissues and an immortalized esophageal epithelial cell line, respectively. The expression of LINC01133 decreased in a TNM stage- and lifestyle-independent manner. LINC01133 was an independent protective factor and had an anti-tumor effect in the early stage of ESCC development. More importantly, we discovered that drinking status in our cohort impaired the predictive accuracy of LINC01133 for patients with ESCC. Furthermore, a new risk model combining LINC01133 expression, drinking status, and TNM stage provided better survival discrimination compared with three other predictors. CONCLUSIONS: Our data indicate that a loss of LINC01133 expression is a potential poor prognostic biomarker and therapeutic target for ESCC and provide additional prognostic information to improve the outcomes of ESCC patients.

Long noncoding RNA LINC01133 inhibits oral squamous cell carcinoma metastasis through a feedback regulation loop with GDF15.

BACKGROUND AND OBJECTIVES: Long noncoding RNAs (lncRNAs) play key roles in carcinoma metastasis. We aimed to investigate lncRNA LINC01133 in oral squamous cell carcinoma (OSCC) metastasis. METHODS: The RNA levels of LINC01133 and growth and differentiation factor 15 (GDF15) in tissue samples from OSCC patients, and OSCC cell lines were tested by real-time quantitative polymerase chain reaction (RT-qPCR). SPSS20.0 was used to perform statistical analysis of LINC01133 expression in clinical samples and correlate expression of LINC01133 and GDF15. Cell migration/invasion was assessed via transwell assays. Downstream genes of LINC01133 were screened using RNA-seq and validated by RT-qPCR. GDF15 protein levels were evaluated via Western blot analysis. RESULTS: LINC01133 was downregulated in OSCCs; higher expression of LINC01133 in OSCCs was correlated with less metastasis and better prognosis. LINC01133 inhibited OSCC cell migration and invasion. RNA-seq data showed that LINC01133 inhibited GDF15, and GDF15 could rescue inhibition of OSCC cell migration and invasion caused by LINC01133. Interestingly, GDF15 also inhibited LINC01133. Furthermore, a significant negative correlation between expression of LINC01133 and GDF15 was validated in the clinical study. CONCLUSIONS: Collectively, these data indicate that LINC01133 inhibited OSCC metastasis via a feedback regulation loop of reciprocal inhibition with GDF15, suggesting a new diagnostic and therapeutic target for OSCC.

A novel long noncoding RNA LINC01133 is upregulated in lung squamous cell cancer and predicts survival.

Lung adenocarcinoma (LAD) and lung squamous cell cancer (LSCC) are two major histological types of non-small cell lung cancer. LSCC differs greatly from LAD in many aspects. Accumulating evidence has shown that long noncoding RNA (lncRNA) plays an important role in the process of carcinogenesis and tumor progression. Expression of lncRNA is highly tissue-specific and could be biomarkers for cancer diagnosis and prognosis. Here, we identified differentially expressed lncRNA between LSCC and LAD by data mining of Affymetrix HG-U133 Plus 2.0 microarray. A set of 1646 differentially expressed lncRNA transcripts were identified. Among these lncRNAs, a novel lncRNA, LINC01133, showed the largest fold change among large intergenic noncoding RNAs. Quantitative real-time polymerase chain reaction (PCR) assay confirmed that LINC01133 was upregulated in LSCC (increasing fold 6.4, P < 0.01) but not in the LAD samples. LSCC patients with higher expression level of LINC01133 had shorter survival time (hazard ratio = 2.383; 95 % confidence interval 1.023-5.547, P = 0.044). Wound-healing and transwell assays demonstrated that silence of LINC01133 by small interfering RNA (siRNA) inhibited invasion ability of LSCC cell line. Thus, a set of lncRNA was differentially expressed between LAD and LSCC and could serve as potential biomarkers.

LINC01133 regulates MARCKS expression via sponging miR-30d-5p to promote the development of lung squamous cell carcinoma.

LncRNAs are vital regulators for lung squamous cell carcinoma (LUSC). However, the detailed role that LINC01133 plays in LUSC is unclear. This work sought to explore the potential function of LINC01133.Levels of LINC01133, miR-30d-5p, and MARCKS were separately tested in both tissues and cells using qRT-PCR. Proliferation was assessed through MTT experiment and apoptosis was detected upon flow cytometry. Transwell experiments were implemented to evaluate migratory and invasive abilities. The interaction between two genes was affirmed through luciferase reporter assay and RNA pull-down experiment. Western blotting measured the protein level of MARCKS. Animal models were established and tissues were taken for IHC analysis of MARCKS and Ki67.LINC01133 was elevated in LUSC and its downregulation could suppress proliferation, migration and invasion but induced apoptosis. LINC01133 interacted with and regulated the binding of miR-30d-5p to MARCKS. LINC01133/miR-30d-5p axis mediated proliferation, apoptosis, migration and invasion in LUSC cells, as well as modulated tumor growth in animal models. LINC01133 interacted with miR-30d-5p to modulate MARCKS expression, contributes to promoted cell proliferation, migration, invasion, and inhibited cell apoptosis in vitro, and promoted tumor growth in vivo. These findings could provide possible therapeutic targets in view of LUSC treatment in the future.

Periplaneta americana extract promotes infectious diabetic ulcers wound healing by downregulation of LINC01133/SLAMF9.

Wound healing in diabetic ulcers remains a significant clinical challenge, primarily due to bacterial infection and impaired angiogenesis. Periplaneta americana extract (PAE) has been widely used to treat diabetic wounds, yet its underlying mechanisms are not fully understood. This study aimed to elucidate these mechanisms by analyzing long non-coding RNA (lncRNA) expressions in the wound tissues from diabetic anal fistula patients treated with or without PAE, using high-throughput sequencing. Peripheral blood monocytes from patients were differentiated into M0 macrophages with human macrophage colony-stimulating factor (hM-CSF) and subsequently polarized into M1 macrophages with lipopolysaccharide. The results indicated that LINC01133 and SLAMF9 were downregulated in wound tissues of patients treated with PAE. Furthermore, PAE suppressed M1 macrophage polarization and enhanced human umbilical vein endothelial cell (HUVEC) proliferation, migration, and angiogenesis. These effects were diminished when LINC01133 or SLAMF9 were overexpressed. Mechanistically, LINC01133 was shown to upregulate SLAMF9 through interaction with ELAVL1. Overexpression of SLAMF9 reversed the effects of LINC01133 silencing on macrophage polarization and HUVEC functions. In conclusion, PAE facilitates the healing of infected diabetic ulcers by downregulating the LINC01133/SLAMF9 pathway.

A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis.

PURPOSE: Pancreatic adenocarcinoma (PAAD) remains a highly aggressive gastrointestinal malignancy with a dismal prognosis. Pyroptosis has a key role in tumor development. Long noncoding RNAs (lncRNAs) are involved in tumorigenesis and pyroptosis regulation. However, the prognostic potential and function of pyroptosis-related lncRNAs (PRLs) in PAAD remain unclear. We aimed to identify PRLs with promising predictive value for PAAD prognosis and investigate the mechanism by which PRLs affect pyroptosis and PAAD development. METHODS: Key genes that regulate pyroptosis were determined from previous studies, and PRLs were identified from lncRNAs shown to be co-expressed in The Cancer Genome Atlas. Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model was used to establish a prognostic PRL signature. The clinical significance and functional mechanisms of LINC01133 were explored in vitro and in vivo. RESULTS: A seven-lncRNA signature was established and the high-risk subgroup exhibited a shorter survival time. With lower immune infiltration abundance, poor immune function, and higher tumor mutational burden (TMB), the high-risk subgroup reflected a more immunosuppressive status with a greater scope for benefiting from immunotherapy. After LINC01133 knockdown, PAAD cells showed lower viability and higher pyroptosis-related gene expression. LINC01133 functioned as a competing endogenous RNA to sequester miR-30b-5p from sponging SIRT1 mRNA to inhibit PAAD pyroptosis. CONCLUSION: With significant prognostic value, our PRL signature are involved in the biological processes of PAAD cells and associated with the immune environment. LINC01133 suppresses pyroptosis to promote PAAD development and could serve as a potential target for PAAD treatment.

Linc01133 promotes proliferation and metastasis of human renal cell carcinoma through sponging miR-760.

Renal cell carcinoma (RCC) is one of the most frequent human tumors and has brought great threats to the health of the people around the globe. It was reported that linc01133, a long non-coding RNA (lncRNA), was involved in the pathogenesis and development of several human cancer. But the biological role of linc01133 in RCC is still not understood. The present study aimed to investigate the biological functions of linc01133 in RCC. We did some biological experiments in this study, including quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, MTT assay, wound healing assay, Transwell invasion assay and xenograft tumor assay. In this study, we found the expression levels of linc01133 markedly increased in the RCC tissues compared with the normal tissues. And we found that the over-expressing of linc01133 promoted cell proliferation, migration and invasion, the interfering of linc01133 inhibited cell proliferation, migration and invasion. Furthermore, we found that the interfering of linc01133 inhibited tumor growth in murine xenograft models. Additionally, we found that linc01133 promotes RCC cell proliferation, migration and invasion through sponging miR-760. Collectively, our work preliminarily illuminated the tumor-promoting role of linc01133 in RCC and the potential molecular mechanism. Thus, our study may provide some evidence for the treatment of RCC.

New Sights Into Long Non-Coding RNA LINC01133 in Cancer.

LINC01133 is a long intergenic non-coding RNA that regulates malignancy in several cancers, including those of the digestive, female reproductive, respiratory, and urinary system. LINC01133 is an extensively studied lncRNA that is highly conserved, and its relatively stable expression is essential for its robust biological function. Its expression is highly tissue-specific with a distinct subcellular localization. It functions as an oncogene or a tumor suppressor gene in different cancers via multiple mechanisms, such as those that involve competing with endogenous RNA and binding to RNA-binding proteins or DNA. Moreover, the secretion and transportation of LINC01133 by extracellular vesicles in the tumor micro-environment is regulated by other cells in the tumor micro-environment. To date, two mechanisms, an increase in copy number and regulation of transcription elements, have been found to regulate LINC01133 expression. Clinically, LINC01133 is an ideal marker for cancer prognosis and a potential therapeutic target in cancer treatment regimes. In this review, we aimed to summarize the aforementioned information as well as posit future directions for LINC01133 research.

Clinical potential of long non-coding RNA LINC01133 as a promising biomarker and therapeutic target in cancers.

Recently, long intergenic non-protein coding RNA 01133 (LINC01133) was identified as a novel transcript in cancers. It modulates various hallmarks of cancers and acts as oncogenic in some cancers while tumor-suppressive in others. Furthermore, the expression of LINC01133 correlates with tumor size, advanced tumor node metastasis stage and lymphatic node metastasis, Ki-67 levels and overall survival of patients. Herein, the authors provide an in-depth analysis describing how LINC01133 modulates the multiple cancer-associated signaling pathways and the pathogenesis of various malignancies and treatment regimens. Based on the role played by LINC01133, the authors propose LINC01133 as both a potential biomarker and a therapeutic target in cancer.

Role of LINC01133 in Osteogenic Differentiation of Dental Pulp Stem Cells by Targeting miR-199b-5p.

PURPOSE: Recently, increasing attention has been paid to the function of long non-coding RNAs (lncRNAs) in osteogenic differentiation (OD) of dental pulp stem cells (DPSCs). LINC01133 was reported to have a close relationship with tumorigenesis for multiple cancers, but no study has yet explored the role of LINC01133 in modulating OD of DPSCs. MATERIALS AND METHODS: Alizarin red S (ARS) staining and alkaline phosphatase (ALP) staining were perfomed to assess the OD potential of DPSCs. Osteogenic markers including runt-related transcription factor 2 (RUNX2), osterix (OSX) and ALP expression levels in DPSCs were monitored by qRT-PCR and Western blot before and after cell transfection. Luciferase reporter gene assay detected the relationship between LINC01133 and miR-199b-5p. RESULTS: The expression of LINC01133 was low, while miR-199b-5p was increasingly expressed during OD of DPSCs. Overexpression of LINC01133 in DPSCs resulted in decreased expression of RUNX2, OSX, ALP, DSPP and DMP1, whose expression was reversed in DPSCs after transfections of miR-199b-5p overexpression. Co-transfection of pcDNA3.1-LINC01133 and miR-199b-5p mimic led to elevated expression of RUNX2, OSX, ALP, DSPP and DMP1 compared with pcDNA3.1-LINC01133 transfection alone. LINC01133 served as a sponge of miR-199b-5p. AKT3 was verified as a downstream effector of miR-199b-5p in DPSCs. CONCLUSION: LINC01133 inhibits the OD of DPSCs by upregulating AKT3 via sponging miR-199b-5p, which may act as a potential diagnostic biomarker for dentin regeneration in the dental pulp.

Long non-coding RNA Linc01133 promotes osteogenic differentiation of human periodontal ligament stem cells via microRNA-30c / bone gamma-carboxyglutamate protein axis.

Periodontitis is a chronic inflammation caused by the deposition of dental plaque on the tooth surface. Human periodontal ligament stem cells (hPDLSCs) have the potential of osteogenic differentiation. Long non-coding RNAs (lncRNAs) are collectively involved in periodontitis. This study was designed to explore the roles of Linc01133 in osteogenic differentiation of hPDLSCs. hPDLSCs obtained from the periodontal ligament (PDL) of patients with periodontitis were used to collect Linc01133, microRNA-30c (miR-30c), and bone gamma-carboxyglutamate protein (BGLAP) expression data, and their expression changes were traced during osteogenic differentiation of hPDLSCs. Quantitative reverse-transcription polymerase chain reaction as well as western blotting were used to analyze the levels of RNAs and proteins. Dual-luciferase reporter and RNA pull-down assays demonstrated the relationship between Linc01133, miR-30c, and BGLAP. Furthermore, alkaline phosphatase (ALP) staining and alizarin red staining were applied to evaluate the degree of osteogenic differentiation. Linc01133 was downregulated in the PDL of patients with periodontitis. Upregulated Linc01133 promoted osteogenic differentiation of hPDLSCs. Linc01133 could inhibit miR-30c expression by sponging miR-30c. miR-30c suppressed osteogenic differentiation. Additionally, miR-30c targeted BGLAP. Knockdown of BGLAP abrogated the effects of decreased miR-30c on osteogenic differentiation of hPDLSCs. Linc01133 acted as a ceRNA to regulate osteogenic differentiation of hPDLSCs via the miR-30c/BGLAP axis. Therefore, Linc01133 may participate in the progress of periodontitis.