scholarly journals Potential prognostic value of hsa-miR-18a in hepatocellular carcinoma and the underlying key down-stream gene CHRM2: a comprehensive bioinformatic analysis*

2021 ◽  
Author(s):  
Zile Fu ◽  
Shuzhan Wen ◽  
Tianchang Wei ◽  
Ruiqi Gu ◽  
Shuying Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Survival Analysis ◽  
Signaling Pathway ◽  
Target Genes ◽  
Differential Expression Analysis ◽  
Bioinformatic Analysis ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Pubmed Database

Abstract Background Hepatocellular carcinoma (HCC) is still the fourth leading cause of cancer-related death. Better prognosticators are warranted for HCC. Hsa-miR-18a has been considered implicated in the pathogenesis of several tumors including HCC. Methods Bioinformatic analyses were conducted to predict target genes and carry out enrichment analysis. Validated downstream genes of hsa-miR-18a were obtained from PubMed database. Differential expression analysis was conducted within the “edgeR” R package based on the TCGA datasets. Survival analysis was performed by Kaplan-Meier survival analysis. All the visualizations were implemented by R. Results Bioinformatic analysis obtained a total of 90 target genes of hsa-miR-18a and revealed that target genes were involved in pathways essential for cancer onset and development such as cell cycle and PI3K/AKT signaling pathway. A review of literatures found target genes of miR-18a indeed participating in the biological processes of HCC. CHRM2 was identified as a special gene after the intersection analysis of TCGA differentially expressed genes (DEGs) and predicted target genes. Survival analysis validated that hsa-miR-18a and CHRM2 significantly affected the prognosis of HCC patients. Conclusion There is a strong association between hsa-miR-18a with tumors including HCC via participating essential tumor-promoting pathways including cell cycle, PI3K/AKT signaling pathway, etc. Furthermore, high miR-18a expression and low CHRM2 expression could lead to a poor prognosis in HCC. In conclusion, miR-18a could serve as an expectational prognostic biomarker in HCC.

scholarly journals SCUBE3 Downregulation Modulates Hepatocellular Carcinoma By Inhibiting CCNE1 Via TGFβ/PI3K/AKT/GSK3β Pathway

2021 ◽  
Author(s):  
Pan xu ◽  
Aoran Luo ◽  
Chuan Xiong ◽  
Hong Ren ◽  
Yan Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Akt Signaling ◽  
Cell Counting ◽  
Pathway Enrichment Analysis ◽  
Akt Signaling Pathway

Abstract Objectives: We aimed to verify the role of signal peptide-CUB-EGF-like domain-containing protein3 (SCUBE3) in the hepatocellular carcinoma (HCC) progression.Methods: The role·of SCUBE3 in HCC cell proliferation, apoptosis, and cell cycle in vitro were investigated using MTT assay, 5-ethynyl-2´-deoxyuridine assay (EDU), Celigo cell counting assay, Caspase3/7 activity assay, and flow cytometry. The effect of SCUBE3 on HCC cell proliferation in vivo was investigated by a xenograft tumor model in nude mice. The related mechanisms were further investigated.Results: SCUBE3 was upregulated in HCC tissues and cell lines. Knockdown of SCUBE3 inhibited proliferation, promoted apoptosis, and induced cell cycle arrest in HCC cell lines in vitro and vivo. Screening of cell cycle-related proteins revealed CCNL2, CDK6, CCNE1, and CCND1 exhibited a significantly different expression profile. We found that SCUBE3 may promote the proliferation of HCC cells by regulating CCNE1 expression. The pathway enrichment analysis showed that the TGFβ signaling pathway and the PI3K/AKT signaling pathway were significantly altered. Co-immunoprecipitation results showed that SCUBE3 binds to the TGFβRII receptor. SCUBE3 knockdown inhibited the PI3K/AKT signaling pathway and the phosphorylation of GSK3β to inhibit its kinase activity.Conclusions：SCUBE3 promotes HCC development by regulating CCNE1 via TGFβ/PI3K/AKT/GSK3βpathway. In addition, SCUBE3 may be a new molecular target for clinical diagnosis and treatment of HCC.

scholarly journals The tRNA-derived fragment 5026a inhibits the proliferation of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Linwen Zhu ◽  
Zhe Li ◽  
Xiuchong Yu ◽  
Yao Ruan ◽  
Yijing Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Qrt Pcr

Abstract Background Recently, tRNA-derived fragments (tRFs) have been shown to serve important biological functions. However, the role of tRFs in gastric cancer has not been fully elucidated. This study aimed to identify the tumor suppressor role of tRF-5026a (tRF-18-79MP9P04) in gastric cancer. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was first used to detect tRF-5026a expression levels in gastric cancer tissues and patient plasma. Next, the relationship between tRF-5026a levels and clinicopathological features in gastric cancer patients was assessed. Cell lines with varying tRF-5026a levels were assessed by measuring tRF-5026a using qRT-PCR. After transfecting cell lines with a tRF-5026a mimic or inhibitor, cell proliferation, colony formation, migration, apoptosis, and cell cycle were evaluated. The expression levels of related proteins in the PTEN/PI3K/AKT pathway were also analyzed by Western blotting. Finally, the effect of tRF-5026a on tumor growth was tested using subcutaneous tumor models in nude mice. Results tRF-5026a was downregulated in gastric cancer patient tissues and plasma samples. tRF-5026a levels were closely related to tumor size, had a certain diagnostic value, and could be used to predict overall survival. tRF-5026a was also downregulated in gastric cancer cell lines. tRF-5026a inhibited the proliferation, migration, and cell cycle progression of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway. Animal experiments showed that upregulation of tRF-5026a effectively inhibited tumor growth. Conclusions tRF-5026a (tRF-18-79MP9P04) is a promising biomarker for gastric cancer diagnostics and has tumor suppressor effects mediated through the PTEN/PI3K/AKT signaling pathway.

scholarly journals Silencing of lncRNA UCA1 inhibited the pathological progression in PCOS mice through the regulation of PI3K/AKT signaling pathway

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Dongyong Yang ◽  
Yanqing Wang ◽  
Yajing Zheng ◽  
Fangfang Dai ◽  
Shiyi Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Structural Damage ◽  
Polycystic Ovary ◽  
Serum Insulin ◽  
Tumor Cell Line ◽  
Akt Signaling ◽  
Akt Signaling Pathway

Abstract Background Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-aged women worldwide, however, the mechanisms and progression of PCOS still unclear due to its heterogeneous nature. Using the human granulosa-like tumor cell line (KGN) and PCOS mice model, we explored the function of lncRNA UCA1 in the pathological progression of PCOS. Results CCK8 assay and Flow cytometry were used to do the cell cycle, apoptosis and proliferation analysis, the results showed that UCA1 knockdown in KGN cells inhibited cell proliferation by blocking cell cycle progression and promoted cell apoptosis. In the in vivo experiment, the ovary of PCOS mice was injected with lentivirus carrying sh-UCA1, the results showed that knockdown of lncRNA UCA1 attenuated the ovary structural damage, increased the number of granular cells, inhibited serum insulin and testosterone release, and reduced the pro-inflammatory cytokine production. Western blot also revealed that UCA1 knockdown in PCOS mice repressed AKT activation, inhibitor experiment demonstrated that suppression of AKT signaling pathway, inhibited the cell proliferation and promoted apoptosis. Conclusions Our study revealed that, in vitro, UCA1 knockdown influenced the apoptosis and proliferation of KGN cells, in vivo, silencing of UCA1 regulated the ovary structural damage, serum insulin release, pro-inflammatory production, and AKT signaling pathway activation, suggesting lncRNA UCA1 plays an important role in the pathological progression of PCOS.

miR-340 Inhibits the Development of Hepatocellular Carcinoma by Down-Regulating Akt Signaling Pathway

2021 ◽  
Vol 11 (9) ◽  
pp. 1785-1791
Author(s):  
Tangpeng Xu ◽  
Changli Ruan ◽  
Xu Bin ◽  
Mengxue Hu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Pathological Grade ◽  
Akt Signaling Pathway ◽  
Invasion And Migration ◽  
Proliferation Ability ◽  
And Migration ◽  
Cancer Tissues

Hepatocellular carcinoma (HCC) is a serious threat to human health. miR-340 participates in HCC pathogenesis, but its specific mechanism is not completely clear. Therefore, our study assessed the mechanism by how miR-340 involves in HCC. The cancer tissues and paracancerous tissues of HCC patients were collected. miR-340 mimics/NC and Akt siRNA were transfected into HepG2 cells followed by analysis of miR-304 and EMT-related molecules expression by Real-time PCR, cell invasion and migration by Transwell assay, cell proliferation ability by CCK8 assay as well as p-Akt and p-mTOR level by Western blot. miR-340 in HCC tissues was significantly downregulated compared to adjacent tissues (P <0.001). With increased pathological grade, miR-340 expression was decreased gradually. p-Akt and p-mTOR in HCC tissues was significantly upregulated and elevated gradually with increased pathological grade. p-Akt and p-mTOR was negatively associated with miR-340 (P <0.001). After overexpression of miR-340, HepG2 cell proliferation, invasion, migration and epithelialization were significantly inhibited, and p-Akt and p-mTOR was reduced. When Akt expression was interfered with siRNA, cell proliferation and epithelialization was further inhibited. miR-340 inhibits the development of hepatocellular carcinoma through Akt signaling pathway.

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