Ribosome Biogenesis and Cancer: Insights into NOB1 and PNO1 Mechanisms.

Post-transcriptional modifications (PTMs) are pivotal in the regulation of gene expression, and pseudouridylation is emerging as a critical player. This modification, facilitated by enzymes such as NOB1 (PNO1), is integral to ribosome biogenesis. PNO1, in collaboration with the NIN1/RPN12 binding protein 1 homolog (NOB1), is vital for the maturation of ribosomes, transitioning 20S pre-rRNA into functional 18S rRNA. Recent studies have highlighted PNO1's potential involvement in cancer progression; however, its underlying mechanisms remain unclear. Relentless growth characterizing cancer underscores the burgeoning significance of epitranscriptomic modifications, including pseudouridylation, in oncogenesis. Given PNO1's emerging role, it is imperative to delineate its contribution to cancer development to identify novel therapeutic interventions. This review summarizes the current literature regarding the role of PNO1 in cancer progression and its molecular underpinnings in oncogenesis. Overexpression of PNO1 was associated with unfavorable prognosis and increased tumor malignancy. At the molecular level, PNO1 facilitates cancer progression by modulating mRNA stability, alternative splicing, and translation efficiency. Its role in pseudouridylation of oncogenic and tumor-suppressor transcripts further underscores its significance in cancer biology. Although disruption of ribosome biogenesis is known to precipitate oncogenesis, the precise mechanisms by which these alterations contribute to cancer remain unclear. This review elucidates the intricate process of ribosomal small subunit maturation, highlighting the roles of crucial ribosomal proteins (RPs) and RNA-binding proteins (RBPs) as well as the positioning and function of NOB1 and PNO1 within the 40S subunit. The involvement of these components in the maturation of the small subunit (SSU) and their significance in the context of cancer therapeutics has been thoroughly explored. PNO1's burgeoning significance in oncology makes it a potential target for cancer therapies. Strategies aimed at modulating PNO1-mediated pseudouridylation may provide new avenues for cancer treatment. However, further research is essential to unravel the complete spectrum of PNO1 mechanisms in cancer and harness this knowledge for the development of targeted and more efficacious anticancer therapies.

Prognostic value of NOB1 expression levels in various cancers: a systematic review and meta-analysis.

Aim: This study evaluates the prognostic significance of NOB1 expression levels in various cancers.Patients & methods: Studies examining NOB1 expression in cancer, encompassing data from 1694 patients across 14 studies, were analyzed for overall survival (OS) and progression-free survival (PFS) using hazard ratios (HRs) and 95% CIs, and for clinicopathological parameters using relative risks (RRs).Results: High NOB1 expression correlated with shorter OS (HR: 2.12, 95% CI: 1.82-2.48) and PFS (HR: 2.23, 95% CI: 1.62-3.07) and was associated with adverse tumor characteristics such as stage and metastasis.Conclusion: Elevated NOB1 expression in various tumors signifies a poor prognosis, serving as a predictive marker for malignancy outcomes.PROSPERO Register Number: CRD42023394051.

This study looked at how a protein called NOB1 affects cancer. NOB1 is usually found in healthy parts of the body like the lungs and liver, but it might also show up in cancer. We checked data from many sources to see if there's a connection between NOB1 and cancer's severity. After studying 1694 samples from 14 studies, we found that people with more NOB1 in their bodies had a tougher time with cancer. Their disease got worse quicker and they did not live as long as those with less NOB1. Also, higher NOB1 levels were linked to more serious and aggressive cancers. This means that NOB1 could help doctors predict how bad a patient's cancer is and plan treatments better.

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway.

OBJECTIVE: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells. METHODS: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues. RESULTS: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05). CONCLUSION: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

miRNA-612 suppresses ovarian cancer cell tumorigenicity by downregulating NOB1.

MicroRNAs (miRNAs) play crucial roles in cancer progression. Our previous study demonstrated that NIN1/RPN12 binding protein 1 homolog (NOB1) was a functional regulator in the progression of ovarian cancer (OC). However, the role of miRNA-612 (miR-612) in OC has not been elucidated. In this study, we aimed to investigate the regulatory mechanism of NOB1 targeting miRNA, miR-612, in OC tumorigenicity. The miR-612 expression was down-regulated in OC patient tissues and four OC cell lines (Caov3, A2780, SKOV3 and OVCAR3). The miR-612 level was negatively correlated with NOB1 expression, and dual-luciferase reporter assay indicated that miR-612 suppressed NOB1 expression by targeting the 3'UTR of NOB1 transcript. Up-regulation of miR-612 mediated by lentiviral transduction suppressed cell proliferation, colony formation, migration, invasion, and induced apoptosis in OC cell lines. In addition, miR-612 overexpression inhibited tumor growth of OC in vivo by sequestering NOB1 expression. In conclusion, our results suggested that miR-612 directly targeted NOB1 to suppress OC progression. Therefore, the miR-612-NOB1 axis could serve as therapeutic targets for OC.

Ribosome assembly factor PNO1 is associated with progression and promotes tumorigenesis in triple­negative breast cancer.

The aim of the present study was to investigate the expression of ribosome assembly factor partner of NOB1 homolog (PNO1) and its association with the progression of breast cancer (BC) in patients, as well as its biological function and underlying mechanism of action in BC cells. Bioinformatics and immunohistochemical analyses revealed that PNO1 expression was significantly increased in BC tissues and its high mRNA expression was associated with shorter overall survival (OS) and relapse­free survival (RFS) of patients with BC, as well as multiple clinical characteristics (including advanced stage of NPI and SBR, etc.) of patients with BC. Biological functional studies revealed that transduction of lentivirus encoding sh­PNO1 significantly downregulated PNO1 expression, reduced cell confluency and the number of BC cells in vitro and inhibited tumor growth in vivo. Moreover, PNO1 knockdown decreased the cell viability and arrested cell cycle progression at the G2/M phase, as well as downregulated cyclin B1 (CCNB1) and cyclin­dependent kinase 1 (CDK1) protein expression in BC cells. Correlation analysis demonstrated that PNO1 expression was positively correlated with both CDK1 and CCNB1 expression in BC samples. Collectively, PNO1 was upregulated in BC and associated with BC patient survival, and PNO1 knockdown suppressed tumor growth in vitro and in vivo. In addition, positive regulation of CCNB1 and CDK1 may be one of the underlying mechanisms.

Expression and distribution of Nob1 in the developing rat cochleae.

BACKGROUND: Mammalian inner ear cells are produced during embryonic development. NIN1/RPN12 binding protein 1 homolog (Nob1), a ribosome assembly factor, is believed to be involved in transcriptional regulation and may play an important role in mediating certain physiological and pathological functions. METHODS: We investigated the expression levels and distribution patterns of Nob1 in rat cochlea at different developmental stages using reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, and immunofluorescence microscopy (P0, P3, P7, P14, and P30, n = 11 per age group). RESULTS: The expression of Nob1 was gradually upregulated from Postnatal day (P) 0 to P14 and stabilized at P30. Our results analyzing Nob1 expression at P0 and P3 in the rat cochleae revealed expression in the greater epithelial ridge cells, lesser epithelial ridge cells, and spiral ganglion neurons (SGNs), whereas low levels of Nob1 expression were observed in the stria vascularis cells. During the development of the cochlea, the organ of Corti undergoes dramatic architectural remodeling. Nob1 expression was stably detected in supporting cells and hair cells from P7 to P30, and its expression gradually increased in the SGNs. CONCLUSIONS: Thus, the present study revealed that upregulation of Nob1 might explain the maturation of the cytoarchitecture in the cochlea during the postnatal period, and a complete understanding of its function in the mammalian inner ear may help to develop strategies to resolve auditory hair cell loss.

Overexpression of microRNA-107 suppressed proliferation, migration, invasion, and the PI3K/Akt signaling pathway and induced apoptosis by targeting Nin one binding (NOB1) protein in a hypopharyngeal squamous cell carcinoma cell line (FaDu).

Hypopharyngeal squamous cell carcinoma (HSCC) is one of the most common head and neck cancers, with a worst prognosis owing to its aggressivity. MicroRNA-107 (miR-107) is reported to regulate the progression of various cancers. Nevertheless, its implied function in HSCC remains unclear. This study is aimed to exploring the roles and potential mechanisms of miR-107 in HSCC. We found that miR-107 expression was significantly decreased in HSCC tissues compared with the para-cancer tissues. Moreover, miR-107 overexpression by miR-107 mimics decreased FaDu cell viability, led to cell cycle arrest in G1/S phase, accelerated apoptosis, and reduced cell migration and invasion. MiR-107 possibly resulted in deactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, evidenced by the decrease of phosphorylated (p-) PI3K and p-Akt. Besides, dual-luciferase reporter assay confirmed that miR-107 might bind to the 3'UTR of Nin one binding protein 1 (NOB1), and elevated NOB1 expression in HSCC tissues and a negative correlation between miR-107 and NOB1 were found. Rescue assays demonstrated the significant roles of miR-107 in FaDu cell behavior by modulating NOB1. In addition, the tumorigenic potential of miR-107 in vivo was conducted. It was found that miR-107 overexpression in FaDu cells significantly inhibited tumor growth and led to inactivation of the PI3K/Akt signaling. The above findings revealed that miR-107 could suppress FaDu cell proliferation, migration, invasion and induced apoptosis by targeting NOB1 through the PI3K/Akt pathway, suggesting that miR-107/NOB1 axis may exert a key role in FaDu HSCC development.

[Retracted] Silencing NOB1 enhances doxorubicin antitumor activity of the papillary thyroid carcinoma in vitro and in vivo.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting assay data shown in Figs. 2 and 5, and the tumour images shown in Fig. 6A, were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 33: 1551-1559, 2015; DOI: 10.3892/or.2015.3730].

LncRNA FEZF1-AS1 aggravates cell proliferation and migration in glioblastoma.

OBJECTIVES: Glioblastoma (GBM) represents the commonest malignant glioma. Long non-coding RNA (lncRNA) FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) has been validated to play an oncogenic role in multiple human malignancies, while its function in GBM has not been largely reported. We aim to identify the regulatory mechanism of FEZF1-AS1 in GBM. MATERIALS & METHODS: The expression pattern of FEZF1-AS1 was firstly figured out in GBM cells using RT-qPCR. Then, functional assays were conducted to examine the influence FEZF1-AS1 had on the biological properties of GBM cells. The downstream targets of FEZF1-AS1 were predicted and the underlying regulatory mechanism was determined by mechanism assays. RESULTS: FEZF1-AS1 possessed high expression in GBM cells. Down-regulation of FEZF1-AS1 suppressed GBM cell proliferation, migration and invasion while inducing cell apoptosis. With the help of bioinformatics prediction and mechanism assays, FEZF1-AS1 was found to bind to miR-363-3p and NOB1 was determined to be the downstream gene. Finally, results of rescue assays verified that the suppressive function of FEZF1-AS1 inhibition on GBM development were restored by miR-363-3p depletion or overexpression of NOB1. CONCLUSION: FEZF1-AS1 had oncogenic function in the advancement of GBM by targeting miR-363-3p/NOB1, which made FEZF1-AS1 a potential biomarker for GBM treatment.

Knockdown of PNO1 inhibits esophageal cancer progression.

The present study aimed to investigate the role of partner of NOB1 homolog (PNO1) in esophageal cancer (EC). The expression levels of PNO1 in EC were primarily analyzed using data obtained from databases. PNO1 expression was also knocked down in EC cells (Eca­109 and TE1) to determine the biological effects of PNO1 on tumorigenesis in vitro and in vivo. In addition, possible downstream targets of PNO1 in EC were identified. The expression levels of PNO1 were upregulated in the tumor tissues compared with that noted in normal tissues. Moreover, the knockdown (KD) of PNO1 suppressed cell proliferation, migration and invasion, and promoted cell apoptosis (P < 0.05). Furthermore, the protein expression levels of AKT1, Twist, Myc, mTOR, matrix metalloproteinase 2 (MMP2), nuclear factor (NF)­κB p65 and ß­catenin 1 (CTNNB1) were downregulated following the KD of PNO1 in Eca­109 cells (P < 0.05). In addition, the overexpression of CTNNB1 reversed the effects of PNO1 KD in Eca­109 cells (P < 0.05). In conclusion, the findings of the present study suggest that PNO1 promotes EC progression by regulating AKT1, Twist, Myc, mTOR, MMP2, NF­κB p65 and CTNNB1 expression.

Aberrant expression of miRNA-192-5p contributes to N,N-dimethylformamide-induced hepatic apoptosis.

Excessive exposure to N,N-dimethylformamide (DMF) can lead to occupational liver poisoning in workers; however, the underlying mechanism is not fully clarified. The importance of microRNAs (miRNAs) in chemical-induced hepatotoxicity has been demonstrated. To determine whether miRNAs are also involved in DMF-induced hepatotoxicity, we systematically analyzed the miRNA expression profiles in DMF-treated (75 and 150 mm) HL-7702 liver cells and controls by high-throughput sequencing. Among the altered miRNAs, miR-192-5p was the most significantly upregulated in HL-7702 cells after DMF exposure and was involved in DMF-mediated cell apoptosis. By contrast, suppression of miR-192-5p in HL-7702 cells attenuated the apoptosis induced by DMF. Furthermore, the anti-apoptotic gene (NIN1/RPN12 binding protein 1 homolog [NOB1]) was predicted to be a potential miR-192-5p target according to bioinformatics analysis. The direct interaction between miR-192-5p and NOB1 was confirmed by the dual-luciferase activity assay in HEK293FT cells. Overexpression of miR-192-5p efficiently reduced NOB1 mRNA and protein expression in HL-7702 cells. Alteration in NOB1 expression influenced DMF-induced hepatotoxicity by affecting hepatic apoptosis. In addition, the inverse correlation between miR-192-5p expression levels and NOB1 expression was further confirmed in DMF-exposed mouse liver tissue samples. These observations demonstrated that promotion of apoptosis from the suppression of NOB1 by miR-192-5p overexpression was responsible for the DMF-induced hepatotoxicity. This work provides the molecular mechanism at the miRNA level for hepatic apoptosis induced by DMF.

MiR-363 suppresses cell migration, invasion, and epithelial-mesenchymal transition of osteosarcoma by binding to NOB1.

BACKGROUND: Osteosarcoma (OS) is a primary malignant bone tumor with a high rate of metastasis and a short 5-year survival rate. MiR-363 was downregulated in a variety of tumors and played a role in suppressing tumors. However, the roles of miR-363 in osteosarcoma remain unknown; thus, the purpose of this study was to explore the functions of miR-363 in osteosarcoma. METHODS: CCK-8 and transwell assays were performed to evaluate the proliferation, migration, and invasion abilities of MG63 cells. The epithelial-mesenchymal transition (EMT) and apoptosis-associated proteins were measured by using Western blot assay. Luciferase reporter assay was utilized to verify whether miR-363 directly bound to the 3'-UTR of NOB1 mRNA. RESULTS: MiR-363 was downregulated while NOB1 was upregulated in osteosarcoma clinical tissue specimens and cell lines as compared with the adjacent normal tissue specimens and normal cell line. The miR-363 is reversely correlated with the expression of NOB1 in osteosarcoma tissues. Overexpression of miR-363 suppressed the ability of cell migration, invasion, and EMT, whereas low expression of miR-363 promoted this ability. In addition, miR-363 inhibited osteosarcoma proliferation both in vitro and in vivo and inhibited the apoptosis in MG63 cells. Interference of NOB1 could inhibit the migration, invasion, and EMT of osteosarcoma cell line MG63. NOB1 was verified to be a direct target of miR-363 and its expression was mediated by miR-363. Re-expression of NOB1 could partially reverse the inhibitory effect of miR-363 on cell migration and invasion. In addition, low expression of miR-363 or overexpression of NOB1 predicted poor prognosis of osteosarcoma patients. CONCLUSION: MiR-363 inhibited osteosarcoma the proliferation, migration, invasion, and EMT and induced the apoptosis by directly targeting NOB1 in MG63 cells. The newly identified miR-363/NOB1 axis provides novel insights into the pathogenesis of osteosarcoma.

NOB1: A Potential Biomarker or Target in Cancer.

Human NIN1/RPN12 binding protein 1 homolog (NOB1), an RNA binding protein, is expressed ubiquitously in normal tissues such as the lung, liver, and spleen. Its core physiological function is to regulate protease activities and participate in maintaining RNA metabolism and stability. NOB1 is overexpressed in a variety of cancers, including pancreatic cancer, non-small cell lung cancer, ovarian cancer, prostate carcinoma, osteosarcoma, papillary thyroid carcinoma, colorectal cancer, and glioma. Although existing data indicate that NOB1 overexpression is associated with cancer growth, invasion, and poor prognosis, the molecular mechanisms behind these effects and its exact roles remain unclear. Several studies have confirmed that NOB1 is clinically relevant in different cancers, and further research at the molecular level will help evaluate the role of NOB1 in tumors. NOB1 has become an attractive target in anticancer therapy because it is overexpressed in many cancers and mediates different stages of tumor development. Elucidating the role of NOB1 in different signaling pathways as a potential cancer treatment will provide new ideas for existing cancer treatment methods. This review summarizes the research progress made into NOB1 in cancer in the past decade; this information provides valuable clues and theoretical guidance for future anticancer therapy by targeting NOB1.

[Eukaryotic translation elongation factor 1A1 positively regulates NOB1 expression to promote invasion and metastasis of hepatocellular carcinoma cells in vitro].

OBJECTIVE: To explore the role of eukaryotic translation elongation factor 1A1 (eEF1A1) in regulating the invasion and metastasis of hepatocellular carcinoma (HCC) cells and the possible mechanism. METHODS: qRT-PCR and Western blotting were used to detect the mRNA and protein expression of eEF1A1 and NOB1 in different HCC cell lines and normal liver cells. The invasion and migration abilities of HCC cells with eEF1A1 knockdown or overexpression were examined using Transwell chamber assay and RTCA assay, and the changes in NOB1 mRNA and protein expressions in the cells were detected. The effects of increasing NOB1 expression in HCCLM3-sheEF1A1 cells and decreasing NOB1 expression in eEF1A1-overexpressing MHCC97h cells on eEF1A1 expression and cell invasion and migration abilities were analyzed using Western blotting, Transwell chamber assay and RTCA assay. RESULTS: The expressions of eEF1A1 and NOB1 were significantly increased in positive correlation in HCC cells as compared with normal hepatocytes. Knockdown of eEF1A1 significantly decreased the invasion and migration of HCC cells and reduced the mRNA and protein expression of NOB1 (P < 0.01). Overexpression of eEF1A1 significantly enhanced invasion and migration of HCC cells and increased NOB1 mRNA and protein expressions (P < 0.01). Increasing NOB1 expression in HCCLM3-sheEF1A1 cells led to the restoration of NOB1 expression and cell invasion and migration abilities (P < 0.01), whereas decreasing NOB1 in MHCC97h-eEF1A1 cells resulted in inhibition of NOB1 expression and cell invasion and migration (P < 0.01). CONCLUSIONS: eEF1A1 positively regulates the expression of NOB1 to promote the invasion and migration of HCC cells in vitro.

Effects of NOB1 on the pathogenesis of osteosarcoma and its expression on the chemosensitivity to cisplatin.

The effects of NIN1/RPN12 binding protein 1 homolog (NOB1) on the pathogenesis of osteosarcoma and its expression on the chemosensitivity to cisplatin were investigated. Seventy-four patients with osteosarcoma who received surgical resection in The Affiliated Hospital of Southwest Medical University (Sichuan, China) from September 2013 to September 2016 were enrolled in this study. The expression of NOB1 in cancer and cancer-adjacent tissues of patients was detected by reverse transcription-polymerase chain reaction, and the relationship between NOB1 expression and the pathogenesis of osteosarcoma was analyzed. The expression of NOB1 in osteosarcoma MG-63 cells was interfered with using small interfering ribonucleic acid (siRNA). Western blotting was used to detect the transfection efficiency and changes in apoptosis indicators. Cell Counting Kit-8 (CCK-8) assay was used to examine changes in the sensitivity of cells to cisplatin. The effect of NOB1 knockout on cell apoptosis was examined by flow cytometry. In patients with osteosarcoma, the level of NOB1 mRNA in cancer tissues was significantly higher than that in cancer-adjacent tissues (p<0.05), and the expression of NOB1 was correlated with Ennecking staging and tumor size (p<0.05). The expression level of the apoptotic indicator caspase-3 was activated after siRNA interfered with NOB1 expression, thus reducing the expression level of anti-apoptotic indicator B-cell lymphoma 2. CCK-8 results showed that the downregulation of NOB1 increased the sensitivity of MG-63 cells to cisplatin (p<0.05). In addition, flow cytometry showed that the downregulation of NOB1 significantly promoted the apoptosis of MG-63 cells. NOB1 is significantly upregulated in patients with osteosarcoma, thus reducing the curative effect of cisplatin chemotherapy, which indicates that the prognosis is poor.

Regulatory effect of NOB1 on osteosarcoma cell-related genes detected by gene microarray technique / 吉林大学学报(医学版)

Objective; To screen the genes may be regulated by NOB1 by using gene microarray technique, and to clarify the regulatory effect of NOB1 on the expression of osteosarcoma cell-related genes. Methods: The U20S cells were treated with lentivirus-mediated RNA interference and to establish the osteosarcoma cells Lv-shN0Bl-U20S. Lv-shCon-U20S group and Lv-shN0Bl-U20S group were set up. The mRNA expressions of those cells were detected using expression pattern analysis. Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to predict the global functions of NOB1, including biological processes, cellular components, molecular functions, and signaling pathways. Results; After NOB1 interference in the U20S cells, there were 792 genes with up-regulated mRNA expression level and 1 059 genes with down-regulated mRNA expression level, with a total variation of 1 851 genes. The GO analysis results showed that from the enrichment degree of cell location entries, the differentially encoded product proteins were mainly distributed on the cell membrane as 56. 9% of the total difference genes, 39. 4% of the totally differential genes distributed in the extracellular region, and 20% of the totally differential genes in the extracellular space; from the enrichment degrees of the molecular function items, the main function of the differentially encoded product proteins was calciu mion binding-related function (22% of the totally differential genes), the second function was transporter activity (9. 2% of the totally differenital genes), and the third function was actin binding activity (8. 7% of the totally differential genes). In terms of the enrichment of biochemical process entries, the main participation process of differentially encoded product proteins was 18. 7% of the totally differential genes of signal transduction, the second involved process was 15. 6% of the totally differential genes produced by multiple organelles, and the third process was the cell adhesion process accounted for 10. 2% of the totally differential genes. The KEGG analysis results showed that their encoding proteins were involved in plasma membrane, calcium ion binding activity and signal transduction. Conclusion; Knockout of NOB1 can affect the expressions of osteosarcoma cell-related genes in an all-round way.

Eukaryotic translation elongation factor 1A1 positively regulates NOB1 expression to promote invasion and metastasis of hepatocellular carcinoma cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the role of eukaryotic translation elongation factor 1A1 (eEF1A1) in regulating the invasion and metastasis of hepatocellular carcinoma (HCC) cells and the possible mechanism.</p><p><b>METHODS</b>qRT-PCR and Western blotting were used to detect the mRNA and protein expression of eEF1A1 and NOB1 in different HCC cell lines and normal liver cells. The invasion and migration abilities of HCC cells with eEF1A1 knockdown or overexpression were examined using Transwell chamber assay and RTCA assay, and the changes in NOB1 mRNA and protein expressions in the cells were detected. The effects of increasing NOB1 expression in HCCLM3-sheEF1A1 cells and decreasing NOB1 expression in eEF1A1-overexpressing MHCC97h cells on eEF1A1 expression and cell invasion and migration abilities were analyzed using Western blotting, Transwell chamber assay and RTCA assay.</p><p><b>RESULTS</b>The expressions of eEF1A1 and NOB1 were significantly increased in positive correlation in HCC cells as compared with normal hepatocytes. Knockdown of eEF1A1 significantly decreased the invasion and migration of HCC cells and reduced the mRNA and protein expression of NOB1 ( < 0.01). Overexpression of eEF1A1 significantly enhanced invasion and migration of HCC cells and increased NOB1 mRNA and protein expressions ( < 0.01). Increasing NOB1 expression in HCCLM3-sheEF1A1 cells led to the restoration of NOB1 expression and cell invasion and migration abilities ( < 0.01), whereas decreasing NOB1 in MHCC97h-eEF1A1 cells resulted in inhibition of NOB1 expression and cell invasion and migration ( < 0.01).</p><p><b>CONCLUSIONS</b>eEF1A1 positively regulates the expression of NOB1 to promote the invasion and migration of HCC cells .</p>

MicroRNA-363 inhibits ovarian cancer progression by inhibiting NOB1.

In this study, we investigated the role of microRNA-363(miR-363) in ovarian cancer (OC) progression. MiR-363expression was downregulated in OC patient tissues and four OC cell lines (SKOV3, A2780, OVCAR and HO-8910). Low miR-363 levels were associated with advanced stage, lymph node metastasis, and poor prognosis in OC. MiR-363 overexpression decreased growth, colony formation, migration and invasiveness of SKOV3 cells. In addition, miR-363 overexpression in SKOV3 cells also decreased xenograft tumor size and weight in nude mice. Bioinformatics and dual luciferase reporter assays revealed that miR-363 suppresses expression of NIN1/RPN12 binding protein 1 homolog (NOB1) by binding to the 3'-UTR of its transcript. NOB1 expression inversely correlated with miR-363 levels in OC tissues. Thus miR-363 appears to play a tumor suppressor role in OC by inhibiting NOB1.

MicroRNA-215 targets NOB1 and inhibits growth and invasion of epithelial ovarian cancer.

MicroRNA-215 (miR-215) has been showed to play crucial roles in tumorigenesis and tumor progression in many types of cancer. However, its biological function and underlying mechanism in epithelial ovarian cancer (EOC) remains greatly unknown. The aims of this study were to investigate biological role and underlying mechanism of miR-215 in EOC. Here, we found that miR-215 expression was significantly decreased in EOC tissues or cell lines compared with adjacent normal tissues or normal ovarian cell line. Decreased miR-215 expression was significantly associated with International Federation of Gynaecology and Obstetrics (FIGO) stage and lymph node metastasis. Function analysis revealed that overexpression of miR-215 using miR-215 mimic significantly inhibit EOC cell proliferation, colony formation, migration and invasion in vitro. as well as suppress tumor growth in vivo. Moreover, we identified ribosome assembly factor NIN/RPN12 binding protein (NOB1) as a direct targets for miR-215 binding, resulting in suppression it expression, which in turn activated the MAPK signaling pathway. In clinical EOC specimens, NOB1 expression was upregulated, and inversely correlated with miR-215 expression (r = -0.675, P<0.001). Overexpression of NOB1 effectively rescued inhibition effect on EOC cells by induced miR-215 overexpression. Taken together, our findings suggested that miR-215 suppressed EOC growth and invasion by targeting NOB1.

Low-level miR-646 in colorectal cancer inhibits cell proliferation and migration by targeting NOB1 expression.

Aberrant expression of microRNA (miRNA) is important in the progression of various human cancers, however further investigation is required in order to fully elucidate mechanisms of and validate actions of endogenous non-coding RNAs. The present study demonstrated that the expression of miR-646 was downregulated in colorectal cancer tissues and cell lines. Notably, it was observed that miR-646, a tumor suppressor, inhibited colorectal cancer cell progression through directly targeting Nin one binding protein (NOB1) expression, which possesses anti-tumor properties in colorectal cancer. Furthermore, knockdown of NOB1 expression was responsible for the tumor-suppressive effect of miR-646. The findings suggest that miR-646 may act as a therapeutic target for the treatment of colorectal cancer.