Hsa_circ_0069094 positively regulates the expression of oncogenic ZNF217 by competitively targeting miR-758–3p to promote the development of breast cancer

To investigate the functions and potential mechanisms of hsa_circ_0069094 in this cancer. The expression of hsa_circ_0069094, zinc finger protein 217 (ZNF217) and microRNA-758–3p (miR-758–3p) was detected by quantitative polymerase chain reaction (qPCR), and the protein level of ZNF217 was detected by western blot. Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay and colony formation assay. Cell cycle progression and cell apoptosis were determined using flow cytometry assay. Cell invasion and cell migration were monitored using transwell assay and wound healing assay. The protein levels of apoptosis-related proteins were quantified by western blot. The putative relationship between miR-758–3p and hsa_circ_0069094 and ZNF217 was confirmed using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft model was constructed in mice to explore the role of hsa_circ_0069094 on solid tumor growth.Hsa_circ_0069094 and ZNF217 were highly expressed, while miR-758–3p was poorly expressed in tissues and cells of breast cancer. Hsa_circ_0069094 knockdown or ZNF217 knockdown inhibited cell proliferation, invasion and migration and induced cell apoptosis and cell cycle arrest in breast cancer cells. The inhibitory effects of hsa_circ_0069094 knockdown on cell malignant behaviors were abolished by ZNF217 overexpression. Hsa_circ_0069094 competed with ZNF217 for the binding site of miR-758–3p, and hsa_circ_0069094 positively regulated ZNF217 expression by competitively binding to miR-758–3p. Hsa_circ_0069094 knockdown also blocked solid tumor growth in mice. Collectively, Hsa_circ_0069094 played oncogenic effects in breast cancer by activating the expression of ZNF217 via competitively binding to miR-758–3p, which might be a novel strategy for breast cancer suppression.     

ZNF746 plays cardinal roles on colorectal cancer (CRC) cell invasion and migration and regulates mitochondrial dynamics and morphological changes of CRC cells—Role of combined melatonin and 5-FU regimen

The underlying mechanism of colorectal cells developing into cancer cells has been extensively investigated, yet is still not fully delineated, resulting in the treatment of advanced colorectal cancer (CRC) remains regrettably an unmet need. Zinc Finger Protein 746/Parkin-interacting substrate (ZNF746/PARIS) has previously been identified to play a fundamental role on bladder cancer cell proliferation and metastasis that were effectively inhibited by melatonin (Mel). In this study, we utilized ex vivo/in vivo studies to verify whether the ZNF746 signaling was also crucial in CRC growth/invasion/migration. Tissue-bank specimens showed that the protein expression of ZNF746 was significantly increased in CRC than that of healthy colorectal tissues (p < 0.001). Additionally, in vitro study demonstrated that excessive expression of ZNF746 significantly inhibited mitochondrial activity via (1) interfering with the dynamic balance of mitochondrial fusion/fission and (2) inhibiting the protein expression of MFN1/MFN2/PGC1a (all p < 0.001). Furthermore, we identified that inhibition of ZNF746 protein expression significantly reduced the resistance of CRC cell lines to the anticancer drug of 5-FU (p < 0.001), whereas overexpression of ZNF746 significantly augmented resistance of CRC cells to 5-FU (all p < 0.001). Finally, using the cell culture method, we found that combined Mel and 5-FU was superior to merely one on promoting the CRC cell apoptosis (p < 0.001). Our results confirmed that ZNF746 signaling played a cardinal role of CRC cell proliferation/survival and combined Mel and 5-FU treatment attenuated the resistance of CRC cells to the drug mainly through suppressing this signaling.     

人锌指蛋白ZNF256基因克隆、表达谱分析及其功能研究

人ZNF256 基因属于C2H2 型锌指蛋白家族.该家族里面的基因大部分为转录因子,它们能够促进细胞分化、参与胚胎及心脏的发育,与精子的形成有关,并且与肿瘤相关.本文采用实时定量 PCR 方法分析了ZNF256 基因在各个组织和不同细胞系中的表达情况,亚细胞定位发现 ZNF256 定位于细胞核,萤光素酶实验分析确定 ZNF256 可以抑制 AP1 的转录活性.这些研究结果为进一步研究 ZNF256 基因在疾病发生中的作用奠定了一定的基础.     

ZNF204P is a stemness-associated oncogenic long non-coding RNA in hepatocellular carcinoma

Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSC-markers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification. Pseudogene-derived long non-coding RNAs are useful candidates as intracellular CSC markers - factors that regulate pluripotency and self-renewal – given their cancer-specific expression and versatile regulation across several levels. Here, we present the use of microarray data to identify stemness-associated factors in liver cancer, and selection of sole pseudogene-derived lncRNA ZNF204P for experimental validation. ZNF204P knockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4 and SOX2, well-known drivers of pluripotency and self-renewal, we propose that ZNF204P promotes tumorigenesis through the miRNA-145-5p/OCT4, SOX2 axis.     

Generation of cells that ignore the effects of PIP3 on cytoskeleton

Comment on: Tang M, et al. Mol Biol Cell 2011; 22:437-47.     

Circular RNA hsa_circ_0008003 facilitates tumorigenesis and development of non‐small cell lung carcinoma via modulating miR‐488/ZNF281 axis

As one of the most aggressive malignancies, non‐small cell lung carcinoma (NSCLC) has high risks of death. It has been demonstrated that circRNAs accelerate NSCLC progression, but the underlying molecular mechanisms of circRNAs in NSCLC were still obscure. In the first place, the circRNA microarray of NSCLC was investigated in this study, and hsa_circ_0008003 (circ‐0008003) was chosen as the research object. Then, it was unveiled that the expression of circ‐0008003 examined via qRT‐PCR was elevated in tumour tissues relative to the non‐tumour tissues, which was associated with TNM stage and lymphatic metastasis in NSCLC. Additionally, the prognosis of NSCLC patients with high circ‐0008003 level was poor. Besides, circ‐0008003 silencing dampened the invasion and proliferation of NSCLC cells. Next, according to the mechanistic studies, circ‐0008003 functioned as a ceRNA of ZNF281 in NSCLC by acting as the endogenous sponge for miR‐488, which was proved to be a tumour suppressor in NSCLC. Additionally, ZNF281 overexpression and miR‐488 suppression recovered the influences of repressed circ‐0008003 on NSCLC cellular processes. It was validated in this research that circ‐0008003 triggered tumour formation in NSCLC, which was adjusted via miR‐488/ZNF281 axis, casting a novel light on the resultful target for treating NSCLC and predicting the prognosis.