LINC00847 drives pancreatic cancer progression by targeting the miR-455-3p/HDAC4 axis.

Introduction: Pancreatic cancer (PC) is a common malignant tumor of the digestive system, posing a serious threat to the life of patients. This study aims to investigate the role of LINC00847 and the LINC00847/miR-455-3p/HDAC4 mechanism in PC progression. Material and methods: The RNA levels of LINC00847, miR-455-3p and HDAC4 were determined by RT-qPCR. HDAC4 protein level was assessed by western blotting. Colony formation and CCK-8 assays were employed to test the proliferation of PC cells. Transwell and scratch assays were conducted to evaluate the cell invasive and migratory abilities, respectively. The effect of LINC00847 silencing on PC cells in vivo was verified using a mouse xenograft model. The correlation among LINC00847, miR-455-3p and HDAC4 was ascertained by dual-luciferase reporter (DLR) assay and Pearson's correlation analysis. Results: The result showed that LINC00847 mainly localized in the cytoplasm was upregulated in PC cells and tissues. Downregulating LINC00847 hindered migration, proliferation, and invasion of PC cells in vitro. Moreover, it also suppressed tumor growth in an in vivo xenograft model. LINC00847 was found to directly target miR-455-3p. miR-455-3p overexpression inhibited cell proliferation and invasion. In addition, HDAC4 was confirmed to be a target gene of miR-455-3p, and HDAC4 overexpression overturned the impact of LINC00847 knockdown on PC cell progression. Conclusions: Our findings reveal that LINC00847 potentially plays a key role in the carcinogenesis of PC progression. This effect may be mediated via regulating the miR-455-3p/HDAC4 axis. This study provides insights into the intricate molecular mechanisms underlying PC and opens avenues for potential therapeutic interventions.

Hsa_circ_0000106 Acts as a Tumor Promoter in Pancreatic Cancer by Targeting the MiR-455-3p/HDAC4.

Circular RNAs (circRNAs) frequently participate in pancreatic cancer (PC) progression. This study focuses on circ_0000106, a novel circRNA, and its potential function in PC development. Circ_00001106, miR-455-3p, and HDAC4 expression levels in PC were determined using qRT-PCR and immunoblotting. RNA immunoprecipitation and dual-luciferase reporter assays were performed to verify their binding interactions. Loss-of-function assays, including CCK-8, colony formation, and transwell assays, were used to estimate the proliferative and migratory properties of PC cells. A nude mouse model was constructed to assess the influence of circ_0000106 on tumor formation in vivo. A pronounced elevation of circ_0000106 and HDAC4 and a reduction of miR-455-3p in PC were observed. Circ_0000106 was prone to binding to miR-455-3p, and miR-455-3p further targeted HDAC4. Functionally, the proliferative and migratory properties of PC cells were dampened by the loss of circ_0000106 or HDAC4 and could be potentiated by miR-455-3p inhibition. Moreover, the knockdown of circ_0000106 delayed tumor growth in vivo. Additionally, the downregulation of miR-455-3p attenuated the repressive effects of circ_0000106 deficiency on PC cell migration and proliferation. Loss of HDAC4 exerted similar mitigative effects on miR-455-3p downregulation-stimulated PC cells. In conclusion, circ_0000106 promotes tumor migration and growth in PC by targeting the miR-455-3p/HDAC4 axis. These results suggest that the circ_0000106/miR-455-3p/HDAC4 network could be regarded as a latent target for PC treatment.

Correlation Analysis of Serum Pepsinogen, Interleukin, and TNF-α with Hp Infection in Patients with Gastric Cancer: A Randomized Parallel Controlled Clinical Study.

Background: Gastric cancer pathological biopsy and visual examination have been the gold standard for gastric cancer diagnosis, but their operation is costly, demanding, and risky, so it is especially important to find an effective examination method in clinical practice. Aims: To investigate the correlation between serum pepsinogen I (PGI), pepsinogen II (PGII), pepsinogen I and II ratio (PGR), IL-6, and TNF-α and Helicobacter pylori (Hp) infection in patients with gastric cancer. Materials and Methods: Fifty patients with Hp-infected gastric cancer admitted to the Department of Gastroenterology of our hospital from January 2019 to December 2021 were selected for the study as the observation group, and another 50 patients without Hp-infected gastric cancer were selected as the comparison group to compare the correlation analysis of PGI, PGII, PGR, IL-6, and TNF-α with Hp infection between the two groups after admission and treatment. Results: After measurement, PGI and PGII in the observation group were significantly lower than those in the comparison group, and TNF-α, IL-18, and IL-6 in the observation group were significantly higher than those in the comparison group, and the comparative differences were all statistically significant (P < 0.05). The results of multivariate logistic regression model analysis of independent risk factors for gastric cancer showed that IL-18, hs-CRP, and tumor necrosis factor- (TNF-) α were risk factors for Hp infection in gastric cancer. Conclusion: The expression of IL-18, hs-CRP, and TNF-α factors in Hp-infected gastric cancer patients is correlated. IL-6, IL-18, and TNF-α are involved in the entire process from the onset to the development of Hp-positive gastric mucosal inflammation in patients, which is of great value in the diagnosis of gastric cancer and helps to assess the degree of progression and prognosis of gastric cancer.

Long non-coding RNA LINC00958 promotes colorectal cancer progression by enhancing the expression of LEM domain containing 1 via microRNA miR-3064-5p.

Colorectal cancer is a common cause of cancer-related death worldwide. Thus, there is an urgent need to determine the mechanism of progression of colorectal cancer. In this study, we investigated the function and mechanism of long non-coding RNA LINC00958, providing a new biomarker for colorectal cancer. The expression of LINC00958, miR-3064-5p, and LEM domain containing 1 (LEMD1) in colorectal cancer tissues and cell lines was analyzed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The interaction between LINC00958, miR-3064-5p, and LEMD1 was assessed using the luciferase assay. The viability, proliferation, migration, invasion, and apoptosis of colorectal cancer cells with silenced LINC00958, miR-3064-5p, and LEMD1 were investigated using the cell counting kit-8 (CCK-8), 5'-Bromo-2'-deoxyuridine (BrdU), flow cytometry, wound healing, and transwell assays. Phosphorylated phosphoinositide 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) protein levels were measured by western blotting. LINC00958 and LEMD1 were found to have increased, while the expression of miR-3064-5p was decreased in colorectal cancer tissues and cell lines. Silencing of LINC00958 hampered cell viability, proliferation, migration, and invasion, while enhancing the apoptosis in colorectal cancer cells. Notably, LINC00958 inhibited miR-3064-5p and promoted LEMD1; the miR-3064-5p inhibitor abrogated the effect of LINC00958 silencing in colorectal cancer cells. Additionally, LEMD1 knockdown inhibited the activation of PI3K/AKT signaling. Our analyses have shown that LINC00958 could facilitate the progression of colorectal cancer by sponging miR-3064-5p and releasing LEMD1, leading to the activation of the PI3K/AKT pathway. Thus, LINC00958 may be considered as an effective biomarker for the treatment of colorectal cancer.

[The effect of rosiglitazone on the activity of STAT1 in rats with severe acute pancreatitis].

OBJECTIVE: To explore the effect of rosiglitazone on the activity of signal transducer and activator of transcription 1 in rats with severe acute pancreatitis. METHODS: Fifty-four male Wistar rats were randomly allocated into three groups (n = 18). SO group: sham-operated animals served as control, operation was executed and sodium chloride but not sodium taurocholate was injected. SAP group: SAP was induced by the retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. ROSI group: same as SAP group, but rosiglitazone (6 mg/kg) was administered intravenously 30 min before operation. Rats in each group were sacrificed at 3,6 and 12 h after operation. The levels of serum amylase and histologic scores of pancreatic tissue were measured. The expression of TNF-alpha mRNA in pancreatic tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR). The expression of phosphorylated STAT1 in pancreatic tissue was assayed by immunohistochemistry. RESULTS: Compared to SO group, the levels of serum amylase and phosphorylated STAT1, TNF-alpha mRNA and histologic scores of pancreatic tissue were significantly elevated at the same time points after SAP (P < 0.01). The levels of these detection in ROSI group were lower than those of the SAP group at the same time points (P < 0.05), but higher than SO group (P < 0.05). CONCLUSIONS: STAT1 was activated in severe acute pancreatitis. Rosiglitazone has a protective effects in rats with severe acute pancreatitis. The mechanism of its protective effects maybe that it inhibits the activation of JAK/STAT pathway, which can down-regulate the expression of TNF-alpha mRNA and block the the inflammatory cascade partially.