Cell Division最新文献

Objective: Hepatocellular carcinoma (HCC) is fatal and poses great challenges to early diagnosis and effective treatment. This paper sought to expound the function of Zinc finger and SCAN domain-containing protein 16 (ZSCAN16) and TBC1 domain family member 31 (TBC1D31) in HCC progression.

Methods: ZSCAN16 and TBC1D31 levels were detected by RT-qPCR, Western blot, and immunohistochemistry. The transcriptional regulation of TBC1D31 by ZSCAN16 was demonstrated by ChIP-qPCR and dual-luciferase assay. Colony formation assay, migration and invasion assays, TUNEL staining, CCK-8 assay, flow cytometry, and western blot analysis were adopted to evaluate the biological activity of HCC cells. The role of the ZSCAN16/TBC1D31 axis in HCC was demonstrated by lentiviral gene intervention combined with functional rescue experiments. Hep3B cells were used to establish a nude mouse xenograft tumor model to study the role of the ZSCAN16/TBC1D31 axis in vivo.

Results: ZSCAN16 and TBC1D31 were highly expressed in HCC. Downregulation of ZSCAN16 repressed the proliferation, migration, and invasion of HCC cells while promoting apoptosis, as well as curbing tumor growth in vivo. Mechanistic studies showed that ZSCAN16 mediated the transcriptional activation of TBC1D31, which in turn led to tumor development. TBC1D31 overexpression reversed the inhibitory effect of ZSCAN16 knockdown on the malignant behavior and tumor growth of HCC cells and accelerated tumor development.

Conclusion: ZSCAN16 mediates transcriptional activation of TBC1D31 and promotes HCC progression.

Glioblastomas (GBM) are most common types of primary brain tumors and miRNAs play an important role in pathogenesis of glioblastomas. Here, we reported a new miRNA, miR-3154, which regulates glioblastoma proliferation and metastasis. miR-3154 was elevated in glioblastoma tissue and cell lines, and its elevation was associated with grade of glioblastomas. Knockdown of miR-3154 in cell lines weakened ability of proliferation and colony formation, and caused cell cycle arrested and higher percentage of apoptosis. Knockdown of miR-3154 also impaired ability of migration and invasion in glioblastoma cells. In mechanism, miR-3154 bound directly to Tumor Protein P53 Inducible Nuclear Protein 1 (TP53INP1), down-regulating TP53INP1 expression at both mRNA and protein level. Silence of TP53INP1 reversed the effect of miR-3154 knockdown on proliferation and metastasis of glioblastoma cells. These findings show that miR-3154 promotes glioblastoma proliferation and metastasis via targeting TP53INP1.

Background: Recent studies have highlighted the role of miR-5195-3p in suppressing cell growth in various cancers. However, the specific functional impact of miR-5195-3p in colorectal cancer (CRC) remain to be fully clarified. The importance of miR-5195-3p in CRC was evaluated, aiming to uncover its underlying molecular mechanism and identify it as a potential therapeutic target for CRC.

Results: Our research has shown that miR-5195-3p is markedly under-expressed in CRC tissues and cell cultures, with its reduced presence associated with a higher TNM stage, lymphatic invasion, and unfavorable survival outcome. Ectopic miR-5195-3p expression curtailed proliferation, migration, and invasion of SW1116 and HT29 cells. Additionally, we discovered that miR-5195-3p directly targets and negatively influences Toll-like receptor 4 (TLR4) in CRC cells. Moreover, an inverse relationship was noted between miR-5195-3p and TLR4 expression in CRC tissue samples. Notably, restoring TLR4 expression counteracted miR-5195-3p's suppressive impact on cell growth, motility, invasiveness, epithelial-mesenchymal transition (EMT), and the TLR4/MyD88 signaling pathway in SW1116 and HT29 cells.

Conclusions: MiR-5195-3p suppresses the CRC cellular functions through the downregulation of TLR4/MyD88 signaling, indicating that targeting miR-5195-3p might offer a viable therapeutic strategy for CRC.

Ovarian cancer (OC) becomes a fatal gynecologic malignant cancer in females worldwide. Target therapy is a promising therapeutical choice for patients with OC, and identifying biomarkers and exploring molecular mechanisms are necessary. In this study, the functions and mechanism of long noncoding RNA transient receptor potential cation channel subfamily M member 2 antisense RNA (TRPM2-AS) in OC were explored. TRPM2-AS expression in OC cells was analyzed utilizing reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 (CCK-8) and colony forming assays were carried out to explore the influence of TRPM2-AS on OC cell viability and proliferation. Cell apoptosis was detected using TdT-mediated dUTP Nick-End labeling (TUNEL) and flow cytometry analysis. Protein expression of apoptotic markers was subjected to western blotting. RNA pulldown or luciferase reporter assays were applied to explore the interaction between TRPM2-AS and miR-6764-5p or the binding of miR-6764-5p and TRPM2. The results showed that TRPM2-AS is highly expressed in OC cells and was mainly localized in cytoplasm. TRPM2-AS depletion suppressed OC cell viability and proliferation while increasing cell apoptotic rate. TRPM2 displayed a high level in OC cells and was positively regulated by TRPM2-AS. TRPM2-AS interacted with miR-6764-5p and thereby upregulated TRPM2 expression. In addition, TRPM2 overexpression reversed the repressive impact of TRPM2-AS depletion on malignant OC cellular process. In conclusion, TRPM2-AS promotes OC cell viability and proliferation while enhancing cell apoptosis through interaction with miR-6764-5p to regulate TRPM2 level.

Background: Nuclear-enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), has been implicated in the colorectal cancer (CRC) progression. However, its upstream mechanism has not been well studied. In the present study, the functions and mechanisms of NEAT1 in CRC were investigated.

Methods: The NEAT1 expression in CRC tissues and CRC cells was analyzed by RT-qPCR. The genes co-expressed with NEAT1 in CRC were obtained from UALCAN, which were intersected with the transcription factors targeting NEAT1 from hTFtarget. Dual-luciferase assay, RT-qPCR, and ChIP were conducted to analyze the transcriptional regulatory relationship between BHLHE40 and NEAT1. LoVo and HCT-15 cells knocking down BHLHE40 and overexpressing NEAT1 were subjected to MTT, Transwell, Western blot, and flow cytometry to examine the malignant aggressiveness of CRC cells. The effects of knocking down BHLHE40 and overexpressing NEAT1 on tumor and lung metastasis were investigated in mice using HE and immunohistochemical analyses.

Results: NEAT1 and BHLHE40 were significantly overexpressed in CRC tissues and cells. BHLHE40 has a binding relationship with the NEAT1 promoter. Knockdown of BHLHE40 resulted in a reverted malignant phenotype in vitro and slowed tumor growth and metastasis dissemination in vivo, which were reversed by NEAT1 overexpression. Overexpression of BHLHE40 increased Wnt/β-catenin pathway activity, but knockdown of NEAT1 decreased Wnt/β-catenin pathway activity.

Conclusions: BHLHE40 mediates the transcriptional activation of NEAT1, which activates the Wnt/β-catenin pathway and promotes the CRC progression.

Nitrogen permease regulator-like 2 (NPRL2/TUSC4) is known to exert both tumor-suppressing and oncogenic effects in different types of cancers, suggesting that its actions are context dependent. Here, we delineated the molecular and functional effects of NPRL2 in malignantly transformed bronchial epithelial cells. To do so, we depleted NPRL2 in oncogenic HRas-transduced and malignantly transformed human bronchial epithelial (BEAS2B), Ras-AI-T2 cells. Intriguingly, depletion of NPRL2 in these cells induced activation of mTORC1 downstream signaling, inhibited autophagy, and impaired Ras-AI-T2 cell proliferation both in vitro and in vivo. These results suggest that NPRL2 is required for oncogenic HRas-induced cell transformation. Depletion of NPRL2 increased levels of the DNA damage marker γH2AX, the cell cycle inhibitors p21 and p27, and the apoptosis marker cleaved-PARP. These NPRL2-depleted cells first accumulated at G1 and G2, and later exhibited signs of mitotic catastrophe, which implied that NPRL2 depletion may be detrimental to oncogenic HRas-transformed cells. Additionally, NPRL2 depletion reduced heat shock factor 1/heat shock element- and NRF2/antioxidant response element-directed luciferase reporter activities in Ras-AI-T2 cells, indicating that NPRL2 depletion led to the suppression of two key cytoprotective processes in oncogenic HRas-transformed cells. Overall, our data suggest that oncogenic HRas-transduced and malignantly transformed cells may depend on NPRL2 for survival and proliferation, and depletion of NPRL2 also induces a stressed state in these cells.