Effects of mir-195 Targeted Regulation of JAK2 on Proliferation, Invasion, and Apoptosis of Gastric Cancer Cells.

Background: Overexpression of miR-195 can make gastric cancer cells stay in G1/G2 phase. miR-195 has been shown to inhibit gastric cancer cell replication and accelerate cell death by targeting JAK2. However, the relationship between miR-195, JAK2, and gastric cancer is not clear. Objective: To observe the effect of mir-195 regulated by JAK2 on the growth, invasion, and death of gastric cancer cells. Methods: MGC803 and NCI gastric N87 cells were introduced into the negative control sequences of miR-195 and RNA, respectively. To detect the expression of miR-195 in cells, to detect the effect of miR-195 on mitosis and proliferation of tumor cells, to analyze the effect of miR-195 on cell invasion and metastasis, and to detect the regulation of miR-195 on JAK2 expression. Results: The level of miR-195 in miR-195-MIMICS group was significantly higher than that in miR-NC group. The cell survival rate of miR-195 mimic group was lower than that of miR-NC group (P < 0.05). Compared with miR-NC group, the number of cells in G1 phase increased, the cells in G2 phase and S phase decreased, and the proportion of cells in G2 and S phase decreased in miR-195 mimic group. The scratch distance of miR-195 simulator group was larger than that of control group. The number of invasive cells in the miR-195 mimic group was significantly lower than that in the control group. The expression of JAK2 protein in miR-195 mimic group was lower than that in miR-NC group. There was a significant negative correlation between the expression level of miR-195 and JAK2 (rhabdomile 0.326 and record 0.00). There are continuous interaction fragments between JAK2 and miR-195. The luciferase activity of miR-195 mimic and wild type JAK2 sequence expression vector was significantly lower than that of wild type JAK2 sequence expression vector. Conclusion: miR-195 may inhibit the occurrence, metastasis, and invasion of gastric tumor by downregulating the expression of JAK2. miR-195/JAK2 may be a new molecular target for the treatment of gastrointestinal tumors.

LncRNA UCID Promotes Hepatocellular Carcinoma Metastasis via Stabilization of Snail.

BACKGROUND: LncRNAs are functional regulators in tumor progression which act by regulating mRNAs in multiple types of cancer. However, the effect of lnc-UCID on hepatocellular carcinoma (HCC) metastasisremains unclear. METHODS: Lnc-UCID expression was quantified in HCC tissues and HCC cell lines by qRT-PCR. HCC cell lines with lnc-UCID knockdown were established by lentivirus transduction. The migration and invasion abilities of HCC cells were analyzed by Transwell and wound-healing assays. Protein expression of epithelial-mesenchymal transition (EMT)-related factors was examined by Western blot assay. Dual-luciferase assays and actinomycin D treatment were conducted to explore the relationship between lnc-UCID and Snail mRNA. The direct interaction between lnc-UCID and Snail mRNA was subjected to quantification analysis by biotinylated lnc-UCID pulldown assays. Pearson's correlation coefficient was used to analyze correlations between lnc-UCID and Snail expression level in clinical samples. Rescue experiments were performed to uncover the role of Snail in the HCC metastasis process. RESULTS: Lnc-UCID was upregulated in human HCC tissues and HCC cell lines. Lnc-UCID promoted the cells' mobility and invasiveness by enhancing the EMT process of HCC cells. The expression of Snail positively correlated with lnc-UCID abundance, and the interaction between lnc-UCID and Snail mRNA prevented miR-122, miR-203, miR-30b, miR-34a or miR-153 binding to the 3'-UTR of Snail. Transfection of Snail greatly rescued the migration and invasion of HCC cells. CONCLUSION: Lnc-UCID was upregulated in clinical HCC samples and directly interacted with Snail mRNA to enhance the stability of Snail mRNA, thus promoting the EMT process to accelerate HCC metastasis.

Linked Color Imaging Can Improve Detection Rate of Early Gastric Cancer in a High-Risk Population: A Multi-Center Randomized Controlled Clinical Trial.

BACKGROUND: Early diagnosis of gastric cancer is difficult in China due to the lack of a valid method for endoscopic screening. Early gastric cancer, especially flat gastric cancer, lacks specific endoscopic features. Many cases appear to be similar to ordinary gastritis cases under normal white light endoscopy, which can lead to misdiagnosis. AIMS: In order to find a new method to improve detection rate of early gastric cancer in China, we designed a trial to validate linked color imaging (LCI) for screening of early gastric cancer in a high-risk population, as compared to white light imaging (WLI). METHOD: Subjects were randomly allocated to either the LCI + WLI or WLI group and then subjected to gastroscopy and all endoscopies were made after special preparation. All endoscopists had knowledge of this experiment. The main indicator was the rate of detection of gastric neoplastic lesions. The difference in the detection rate between the two groups is reported. RESULTS: The detection rate was 4.31% in the WLI group and 8.01% in the LCI + WLI group. This is a difference of 3.70% with a P value < 0.001 and an OR (95% CI) of 1.934 (1.362, 2.746). The lower limit of the 95% CI was greater than 0, and the superiority margin was 1%. CONCLUSION: The detection rate of gastric neoplastic lesions was higher in the LCI + WLI group than in the WLI group, LCI might be an effective method for screening early gastric cancer.

Silencing DVL3 defeats MTX resistance and attenuates stemness via Notch Signaling Pathway in colorectal cancer.

Chemoresistance and recurrence of colorectal cancer are mainly caused by the existence of cancer stem-like cells. Dishevelled-3 (DVL3) is a common member of both Wnt/ß-catenin pathway and the Notch signaling pathway, which were involved in cancer progression, chemoresistance and even maintenance of stem cell-like properties. However, the underlying biological function of DVL3 still remains unclear. In this study, we proposed DVL3 was simultaneously involved in Methotrexate (MTX) resistance and Colorectal cancer (CRC) stemness by bioinformatic analysis. We also demonstrated DVL3 knockdown sensitized CRC cells to MTX and inhibited their stem cell-like properties by functional experiments. As for the mechanism, DVL3 silencing attenuated the activated Notch signaling by down-regulating Notch intracellular domain (NICD) as well as its downstream targets. Additionally, we demonstrated that CRC cancer tissues had greater DVL3 expression than adjacent non-cancer tissues and patients' overall survival was closely associated with DVL3 according to the data in our clinical center. Accordingly, our data suggest that DVL3 is a key regulator in CRC stemness and chemoresistance and targeting DVL3 could be a potential strategy for CRC therapy.

SLC39A7, regulated by miR-139-5p, induces cell proliferation, migration and inhibits apoptosis in gastric cancer via Akt/mTOR signaling pathway.

As a zinc transporter, SLC39A7 (zip7) is vital in intestinal epithelial self-renewal, and recent studies suggested that SLC39A7 was related to cancer progression. Whereas, little is known about the role of SLC39A7 in gastric cancer (GC). In the present study, qRT-PCR analysis demonstrated that SLC39A7 mRNA level was increased in both GC tissues and cell lines. Overexpressing SLC39A7 boosted cell proliferation and migration, while inhibited apoptosis in GC. It was also found that si-SLC39A7 suppressed Akt/mTOR pathway and activation of Akt/mTOR pathway reversed the effects of si-SLC39A7 on GC development. Through prediction website, we found that SLC39A7 was directly regulated by miR-139-5p. miR-139-5p mimic had adverse effects on SLC39A7 expression and influence in the GC cell proliferation, migration and apoptosis by Akt/mTOR signaling pathway, while miR-139-5p inhibitor showed opposite effects. To conclude, our studies showed that SLC39A7 was negatively regulated by miR-139-5p. Besides, SLC39A7 positively regulated GC development through Akt/mTOR signaling pathway. These results indicate that SLC39A7 may be a candidate target gene for GC treatment.

CSE1L silence inhibits the growth and metastasis in gastric cancer by repressing GPNMB via positively regulating transcription factor MITF.

Human chromosomal segregation 1-like (CSE1L) gene functions as a key molecular mediator in cellular proliferation, invasion, and apoptosis. The association of CSE1L with tumor progression has been reported in diverse human cancers. A greater understanding of CSE1L molecular mechanism is beneficial for cancer treatment. In the current study, we show that CSE1L was highly expressed in gastric cancer (GC) cell lines. CSE1L silence promoted apoptosis and inhibited cell proliferation and invasion. Overexpression of glycoprotein nonmetastatic melanoma protein B (GPNMB) reversed the anticancer effect of CSE1L inhibition. CSE1L inhibition decreased GPNMB by microphthalmia-associated transcription factor (MITF). Moreover, GPNMB regulates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. Taken together, our study revealed that CSE1L inhibition decreased MITF and suppressed GPNMB expression, thereby activating the PI3K/Akt/mTOR and MEK/ERK signaling pathway, ultimately inhibiting the tumor growth and metastasis in GC.