scholarly journals Suppression of Heterogeneous Nuclear Ribonucleoprotein C Inhibit Hepatocellular Carcinoma Proliferation, Migration, and Invasion via Ras/MAPK Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiejun Hu ◽  
Dong Cai ◽  
Zhibo Zhao ◽  
Guo-Chao Zhong ◽  
Jianping Gong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Migration And Invasion ◽  
Advanced Tumor Stage ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Tumor Tissues ◽  
Nuclear Ribonucleoprotein

Hepatocellular carcinoma (HCC), the most common malignant tumor, has high fatality and recurrence rates. Accumulating evidence shows that heterogeneous nuclear ribonucleoprotein C (HNRNPC), which is mainly involved in RNA splicing, export, and translation, promotes progression and metastasis of multiple tumor types; however, the effects of HNRNPC in HCC are unknown. In the present study, high levels of HNRNPC were detected in tumor tissues compared with para-tumor tissues by immunohistochemical and western blot assays. Furthermore, Cox proportional hazards regression models, the Kaplan–Meier method, and clinicopathologic features analysis showed that HNRNPC was not only an independent prognostic factor for both overall and disease-free survival in HCC but also a predictor of large tumor size and advanced tumor stage. Functional experiments revealed that silencing of HNRNPC not only led to arrest of more HCC cells at G0/G1 phase to inhibit their proliferation, but also suppressed EMT process to block their invasion, and migration in vitro; this was related to the Ras/MAPK signaling pathway. In addition, blocking of HCC cell proliferation regulated by HNRNPC silencing was observed in vivo. Finally, rescue tests showed that after recovery of Ras/MAPK signaling pathway activity by treatment with Ras agonists, the proliferation, migration, and invasion suppression of Huh-7 and Hep 3B cell lines caused by HNRNPC knockdown was partially reversed. Taken together, these results indicate that HNRNPC knockdown inhibits HCC cell proliferation, migration and invasion, in part via the Ras/MAPK signaling pathway. Thus, HNRNPC may have an important role in the progression of HCC and represents a promising biomarker for evaluation of prognosis and a potential therapeutic target in HCC patients.

scholarly journals Long noncoding RNA 00976 promotes pancreatic cancer progression through OTUD7B by sponging miR-137 involving EGFR/MAPK pathway

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Shan Lei ◽  
Zhiwei He ◽  
Tengxiang Chen ◽  
Xingjun Guo ◽  
Zhirui Zeng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Migration And Invasion ◽  
Potential Biomarker

Abstract Background Accumulation evidence indicates the vital role of long non-coding RNAs (lncRNAs) in tumorigenesis and the progression of malignant tumors, including pancreatic cancer (PC). However, the role and the molecular mechanism of long non-coding RNA 00976 is unclear in pancreatic cancer. Methods In situ hybridization (ISH) and qRT-PCR was performed to investigate the association between linc00976 expression and the clinicopathological characteristics and prognosis of patients with PC. Subsequently, linc00976 over-expression vector and shRNAs were transfected into PC cells to up-regulate or down-regulate linc00976 expression. Loss- and gain-of function assays were performed to investigate the role of linc00976 in proliferation and metastasis in vitro and vivo. ITRAQ, bioinformatic analysis and rescue assay were used to illustrate the ceRNA mechanism network of linc00976/miR-137/OTUD7B and its downstream EGFR/MAPK signaling pathway. Results linc00976 expression was overexpressed in PC tissues and cell lines and was positively associated with poorer survival in patients with PC. Function studies revealed that linc00976 knockdown significantly suppressed cell proliferation, migration and invasion in vivo and in vitro, whereas its overexpression reversed these effects. Based on Itraq results and online database prediction, Ovarian tumor proteases OTUD7B was found as a downstream gene of linc00976, which deubiquitinated EGFR mediates MAPK signaling activation. Furthermore, Bioinformatics analysis and luciferase assays and rescue experiments revealed that linc00976/miR137/OTUD7B established the ceRNA network modulating PC cell proliferation and tumor growth. Conclusion The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137. Ultimately, OTUD7B mediates EGFR and MAPK signaling pathway, suggesting that linc00976/miR-137/OTUD7B/EGFR axis may act as a potential biomarker and therapeutic target for PC.

scholarly journals mascRNA and its parent lncRNA MALAT1 promote proliferation and metastasis of hepatocellular carcinoma cells by activating ERK/MAPK signaling pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shu-Juan Xie ◽  
Li-Ting Diao ◽  
Nan Cai ◽  
Li-Ting Zhang ◽  
Sha Xiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Mammalian Cells ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Erk Mapk ◽  
Lncrna Malat1 ◽  
Hcc Cells

AbstractMALAT1-associated small cytoplasmic RNA (mascRNA) is a cytoplasmic tRNA-like small RNA derived from nucleus-located long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). While MALAT1 was extensively studied and was found to function in multiple cellular processes, including tumorigenesis and tumor progression, the role of mascRNA was largely unknown. Here we show that mascRNA is upregulated in multiple cancer cell lines and hepatocellular carcinoma (HCC) clinical samples. Using HCC cells as model, we found that mascRNA and its parent lncRNA MALAT1 can both promote cell proliferation, migration, and invasion in vitro. Correspondingly, both of them can enhance the tumor growth in mice subcutaneous tumor model and can promote metastasis by tail intravenous injection of HCC cells. Furthermore, we revealed that mascRNA and MALAT1 can both activate ERK/MAPK signaling pathway, which regulates metastasis-related genes and may contribute to the aggressive phenotype of HCC cells. Our results indicate a coordination in function and mechanism of mascRNA and MALAT1 during development and progress of HCC, and provide a paradigm for deciphering tRNA-like structures and their parent transcripts in mammalian cells.

scholarly journals Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway

2017 ◽  
Vol 41 (5) ◽  
pp. 1851-1864 ◽  
Author(s):  
Ren-hong Huang ◽  
Ying-jun Quan ◽  
Jin-hong Chen ◽  
Ting-feng Wang ◽  
Ming Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Western Blot ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Hct116 Cell ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Cell Counting ◽  
Migration And Invasion

Background: Osteopontin (OPN) is highly expressed in colorectal cancer (CRC) and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to play a significant role in carcinogenesis. However, the mechanisms of OPN's effects on CRC cell autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms of OPN's effects on CRC autophagy. Methods: HCT116 cell proliferation, apoptosis, and migration and invasion ability were identified by cell counting k¡t-8 assay, flow cytometry, wound healing assay, and transwell chamber invasion assay, respectively. The ratios of proteins LC3-II/LC3-I, P62, and Atg7 were analyzed by Western-blot. Expressions of Beclin-1, Atg4b, Bnip3, and Vps34, both in transcriptional and translational levels, were analyzed and compared by RT-PCR and Western blot. Immunofluorescence and co-focusing experiments were used to investigate the formation of autophagosomes. Results: The results showed that OPN can promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis. It was also demonstrated that OPN could inhibit cell autophagy. Further experiments revealed that the inhibitory effect of OPN on autophagy could be reversed by blocking the p38 MAPK pathway in HCT116 cells. Conclusion: OPN is involved in HCT116 cell progression and is capable of inhibiting cell autophagy possibly by activating the p38 MAPK signaling pathway, implying that OPN could be a potential novel molecular therapeutic biomarker in patients with CRC.

microR-505/heterogeneous nuclear ribonucleoprotein M inhibits hepatocellular carcinoma cell proliferation and induces cell apoptosis through the Wnt/β-catenin signaling pathway

2020 ◽  
Vol 14 (11) ◽  
pp. 981-996
Author(s):  
Xiaobin Chi ◽  
Yi Jiang ◽  
Yongbiao Chen ◽  
Lizhi Lv ◽  
Jianwei Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Apoptosis Assay ◽  
Proliferation And Metastasis ◽  
Novel Strategy ◽  
Nuclear Ribonucleoprotein

Aim: This study aimed to investigate the expression of microRNA-505 (miR-505) and explore its clinical significance, biological function and mechanisms in hepatocellular carcinoma (HCC). Methods: Expression of miR-505 was measured in 128 paired HCC tissues and five cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). MTT assay, Transwell migration, invasion assays and apoptosis assay were performed to explore the functional role of miR-505. The target gene of miR-505 was assessed using the bioinformatics assay and the related signaling pathway was confirmed using western blot. Results: Expression of miR-505 in HCC serum and tissues were downregulated. The overexpression of miR-505 in HCC cells inhibited cell proliferation and metastasis, as well as enhanced cell apoptosis by directly downregulating heterogeneous nuclear ribonucleoprotein M ( HNRNPM). The activity of the Wnt/β-catenin signaling pathway was suppressed by the overexpression of miR-505 but was promoted by the upregulation of HNRNPM. Conclusion: The results suggest that the regulation of miR-505/ HNRNPM may be a novel strategy to improve the targeted therapy of HCC.

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