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Background: Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined. Methods: Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1. Results: Significantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC. Conclusions: CCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) are attached to each other in the bone marrow (BM) cavity and in in vitro cultures, and this adhesion has important physiological significance. We demonstrated that cell proliferation could be promoted when MSCs were co-cultured with EPCs, which was beneficial to angiogenesis, tissue repair, and regeneration. The adhesion of MSCs and EPCs could promote the pluripotency of MSCs, particularly self-renewal and multi-differentiation to osteoblasts, chondrocytes, and adipocytes. This study focused on the mechanism of adhesion between EPCs and MSCs. The results showed that E-cadherin (E-cad) mediated the adhesion of MSCs and EPCs through the E-cad/beta-catenin signaling pathway. The E-cad of EPCs occupied a dominant position during this process, which activated and up-regulated the beta-catenin (β-catenin) of MSCs to improve cohesion and exert their biological function. [ABSTRACT FROM AUTHOR]

The SH2 domain-containing phosphatase 2 (SHP2) is a widely expressed protein tyrosine phosphatase, and it is proposed to act as an oncogenic protein. SHP2 is also engaged in drug resistance of a variety of cancers. However, the role of SHP2 in the proliferation and drug resistance of colon cancer cells remains elusive. In this work we determined the effect of SHP2 expression on colon cancer cell proliferation and resistance to oxaliplatin (L-OHP), a commonly used drug in the clinic. Our results show that knockdown of SHP2 decreased and overexpression of SHP2 increased the proliferation of SW480 cells, respectively. Knockdown of SHP2 increased, and overexpression of SHP2 decreased apoptosis of the cells. We selected oxaliplatin-resistant SW480(SW480/L-OHP) and HCT116(HCT116/L-OHP) cells and found that the SHP2 protein level was raised in these drug-resistant cells. The upregulated SHP2 contributed to oxaliplatin resistance of the cells, as knockdown of SHP2 decreased the IC 50 of oxaliplatin and abated proliferation and survival of SW480/L-OHP and HCT116/L-OHP cells in the presence of oxaliplatin. Also, SW480/L-OHP and HCT116/L-OHP cells had increased phosphorylation of AKT and ERK. Inhibition of AKT, ERK, or SHP2 sensitized SW480/L-OHP and HCT116/L-OHP cells to oxaliplatin. Our results indicate that SHP2 contributes oxaliplatin resistance through AKT and ERK. These results also suggest that SHP2-targeting is a potential strategy for overcoming oxaliplatin resistance of colon cancer cells. • SHP2 promote cell proliferation and inhibit cell apoptosis in colon cancer cells. • SHP2 is upregulated in oxaliplatin-resistant colon cancer cells. • SHP2 promote oxaliplatin resistance in colon cancer cells through activating AKT and ERK. [ABSTRACT FROM AUTHOR]

Background: Accumulating studies have demonstrated that the Warburg effect plays a central role in the occurrence and development of hepatocellular carcinoma (HCC), albeit the role of non-coding RNA (lncRNA) in its association remains unclear. Methods: The Zhengzhou University People's Hospital kindly provided 80 pairs of HCC tissues and their matched paracancerous tissues for this study. Bioinformatics analysis, real-time quantitative polymerase chain reaction, Western blotting, and oncology functional assays were performed to determine the contribution of RP11-620J15.3 to the development of HCC. The mechanism of co-immunoprecipitation and a luciferase reporter gene was employed to ascertain how RP11-620J15.3 interacts with important molecular targets. Results: Our results revealed that a lncRNA termed RP11-620J15.3 was overexpressed in HCC and was substantially associated with the tumor size. A high expression of RP11-620J15.3 mRNA was found to be significantly associated with worsening prognosis in HCC patients. We discovered that RP11-620J15.3 stimulated the glycolytic pathway in HCC cells by RNA-sequencing (RNA-seq) and metabolomics analyses. Mechanistically, RP11-620J15.3 acted as a competitive endogenous RNA to regulate the GPI expression by sponging miR-326 in HCC. In addition, TBP acted as a transcription factor for RP11-620J15.3, which contributed to the high expression of RP11-620J15.3 in HCC cells. Conclusion: Based on our findings, lncRNA RP11-620J15.3 is a novel LncRNA that positively regulates tumor progression. Specifically, RP11-620J15.3/miR-326/GPI pathway promotes HCC malignant progression by regulating glycolysis, thereby providing novel targets for HCC treatment and drug development. [ABSTRACT FROM AUTHOR]

Background. Hepatocellular carcinoma (HCC) is one of the most common and fatal malignancies in human beings. Studies have shown that long non-coding RNAs (lncRNAs) play key parts in the occurrence and development of HCC. Although many lncRNAs have been studied in the HCC specifically for DNA damage repair, the role of LINC01419 in cellular DNA damage repair has not yet been studied. Objective. This study is aimed at exploring the biological role of LINC01419 and its potential mechanism in HCC. Methods. qRT-PCR was used to detect the expression level of LINC01419 in HCC tissues and cells, the proteins which were involved were detected by Western blot. Effect of LINC01419 knockdown on cell cycle, apoptosis, DNA damage, cell proliferation, wound healing, colony formation, and migration of HCC cells was studied in vitro. Results. The analysis showed that LINC01419 was overexpressed in HCC tissues and cells. Silencing of LINC01419 expression significantly inhibited the proliferation and migration ability of the HCC cells and resulted in cell cycle arrest at G0/G1 phase. Furthermore, the knockdown of LINC01419 increased the DNA damage, and to some extent, promoted sensitivity of HCC cells to doxorubicin. In addition, we performed RIP analysis which showed XRCC5 as a potential protein related to DNA damage repair in hepatoma cells. Conclusion. In conclusion, the LINC01419 acts as an oncogene in HCC and regulates DNA damage repair through XRCC5 in HCC cells. [ABSTRACT FROM AUTHOR]

Purpose: MYCN amplification and p53 inactivation are two typical characteristics of aggressive neuroblastomas and are strongly associated with cancer progression and treatment failure. In an effort to develop new therapeutic agents to treat the aggressive neuroblastomas, we constructed ZD55-shMYCN, an oncolytic adenovirus ZD55 carrying short hairpin RNA (shRNA) targeting MYCN gene, and investigated the effects on proliferation of the p53-null and MYCN-amplified neuroblastoma cell line LA1-55N in vitro and in vivo by ZD55-shMYCN. Methods: In this study, we used ZD55-shMYCN to treat p53-null and MYCN-amplified neuroblastoma cells. To confirm the ability of selective replication of the ZD55-shMYCN, we examined the expression of E1A protein by western blotting. We used quantitative real-time PCR analysis and western blotting analysis to determine the inhibitory effect of ZD55-shMYCN on MYCN expression. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cell proliferation assay and xenograft mouse model were used to test the antigrowth efficacy of ZD55-shMYCN. Results: The results showed that ZD55-shMYCN selectively replicated and significantly downregulated the MYCN expression in LA1-55N cells. ZD55-shMYCN effectively inhibited the proliferation in LA1-55N cells in vitro and significantly inhibited tumor growth in vivo xenograft tumor in nude mice. Conclusions: ZD55-shMYCN provides a novel agent for treating MYCN-amplified and p53-inactive aggressive neuroblastoma, representing a promising approach for further clinical development. [ABSTRACT FROM AUTHOR]

Substance P (SP) plays an important role in several types of cancer promotion and progression by binding to its preferential neurokinin 1 receptor (NK1R). However, the clinical significance and downstream mechanism of NK1R in esophageal squamous cell carcinoma (ESCC) have not been elucidated. The aim of this study was to investigate the role of SP/NK1R in the proliferation of ESCC and to screen related downstream molecules. In the current investigation, the expression of NK1R was detected via immunohistochemistry (IHC), western blot (WB) analysis and real-time reverse transcription-polymerase chain reaction (RT-qPCR) in ESCC tissues and cell lines. Thereafter, the optimal concentration of SP was determined in vitro. The proliferation ability of SP/NK1R was assessed by cell counting kit-8 (CCK-8) and colony formation assays and subcutaneous tumour formation in nude mice with EC109 cells. Moreover, the related downstream molecules were screened by performing isobaric tags for relative and absolute quantitation (iTRAQ) protein spectrum analysis. NK1R was upregulated in ESCC, and its overexpression correlated with larger tumour size, deeper tumour invasion, more perineural invasion and eventually caused poorer overall survival (OS). Both intrinsic and SP-activated NK1R upregulation could promote the proliferation and clonogenic capacity of ESCC cells. In nude mice, tumour growth was suppressed by EC109 cells of NK1R downregulation. Further experiments demonstrated that Hairy and Enhancer of Split 1 (Hes1) was markedly reduced upon NK1R downregulation in EC109 cell lines and could regulate cell proliferation in the downstream of SP/NK1R. The significant role of NK1R in mediating ESCC cell proliferation depended on the activation of SP and might be related to the downstream regulation of Hes1. • NK1R was overexpressed in ESCC tissues and predicts advanced stage and poorer OS. • SP/NK1R promotes cell proliferation both in vitro and in vivo. • SP/NK1R mediating ESCC cell proliferation via the downstream regulation of Hes1. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most widespread malignant human tumors worldwide. Treatment options include radiotherapy, surgical intervention and chemotherapy; however, drug resistance is an ongoing treatment concern. In the present study, the effects of a microRNA (miR/miRNA), miR-9, on the sensitivity of HCC cell lines to the epidermal growth factor receptor inhibitor, cetuximab, were examined. miR-9 has been proposed to serve a role in tumorigenesis and tumor progression. In the present study, bioinformatics analyses identified the eukaryotic translation initiation factor 5A2 (eIF-5A-2) as a target of miR-9. The expression levels of miR-9 and eIF-5A-2 were examined by reverse transcription-quantitative polymerase chain reaction and HCC cell lines were transfected with miR-9 mimics and inhibitors to determine the effects of the miRNA on cell proliferation and viability. The miR-9 mimic was revealed to significantly increase the sensitivity of epithelial phenotype HCC cells (Hep3B and Huh7) to cetuximab, while the miR-9 inhibitor triggered the opposite effect. There were no significant differences in sensitivity to cetuximab observed in mesenchymal phenotype HCC cells (SNU387 and SNU449). Cells lines displaying high expression levels of eIF-5A-2 were more resistant to cetuximab. Transfection of cells with a miR-9 mimic resulted in downregulation of the expression of eIF-5A-2 mRNA, while an miR-9 inhibitor increased expression. When expression of eIF-5A-2 was knocked down with siRNA, the effects of miR-9 on cetuximab sensitivity were no longer observed. Taken together, these data support a role for miR-9 in enhancing the sensitivity of epithelial phenotype HCC cells to cetuximab through regulation of eIF-5A-2. [ABSTRACT FROM AUTHOR]

Upon ER stress, IRE1α is activated to splice XBP1 mRNA to generate XBP1s, a transcription factor that induces the expression of genes to cope with the stress. Expression of IRE1α is elevated in cancers and the IRE1α-XBP1s axis plays an important role in proliferation of cancer cells. However, the underlying mechanism is not well known. We found that ER stressors induced the expression of IRE1α , which was inhibited by depletion of XBP1s. XBP1s bound IRE1α promoter and initiated the transcription of IRE1α. These data indicate that XBP1s acts as a transcription factor of IRE1α. Overexpression of XBP1s increased the phosphorylation of JNK, a substrate of IRE1α kinase, which was inhibited by IRE1α kinase inhibitor Kira8. Overexpression of XBP1s also activated the regulated IRE1-dependent decay of mRNAs, which was suppressed by IRE1α RNase inhibitor STF083010. Moreover, we found that expression of XBP1s promoted proliferation of colon cancer cells, which was abrogated by Kira8 and STF083010. The results suggest that XBP1s functions to induce IRE1α expression and promote cancer cell proliferation. Our findings reveal a previously unknown mechanism of IRE1α expression by XBP1s and highlight the role of this regulation in proliferation of colon cancer cells, suggesting that IRE1α-targeting is a potential therapeutic strategy for colon cancer. [Display omitted] • ER stress induces the expression of IRE1α through XBP1s. • XBP1s acts as a transcription factor of IRE1α. • XBP1s promotes cell proliferation through IRE1α. [ABSTRACT FROM AUTHOR]

Purposes: Uncontrolled proliferation is a key characteristic of gastric carcinogenesis and the precise mechanisms underlying the altered proliferation behaviors of GC cells have not been clearly elucidated. miRNAs has been suggested to play a crucial role in the pathogenesis and development of various cancers. In the present study, we employed an impedance-based real-time cell electronic sensing (RT-CES) system to detect the effects of ectopically expressed miRNAs on GC cell proliferation. Methods: miRNA mimics were transfected into gastric cancer cell line SGC7901 and the effect of individual miRNA on the proliferation rate of the cells was measured by the RT-CES system. The screening results were validated with qRT-PCR and miR-137 was selected for further research. The effects of ectopically expressed miR-137 on GC cell growth and cell cycle progress were measured using MTT assay and flow cytometry. The target gene of miR-137 was predicted using different bioinformatics tools and the direct interaction between miR-137 and the 3'-UTR was confirmed with a luciferase reporter assay. The in vivo effect of miR-137 on GC cell proliferation was examined with a tumor-bearing nude mouse model. The correlation between miR-137 expression and patients' prognosis was explored in a cohort of 38 patients. Prognosis was explored in a cohort of 38 patients. Results: Ectopic expression of miR-137 was sufficient to inhibit GC cell proliferation both in vitro and in vivo. Bioinformatics prediction and luciferase reporter assay revealed CDK6 as a target gene through which miR-137 exerted an inhibitory function. Moreover, miR-137 expression positively correlated with better prognosis. Conclusion: Our data indicated an important regulatory role of miR-137 in GC cell proliferation and that it may be explored as a prognostic marker for GC. [ABSTRACT FROM AUTHOR]