The role of lncRNA NEAT1 in human cancer chemoresistance.

Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resistance to chemotherapeutic drugs by regulating cell apoptosis, cell cycle, drug transport and metabolism, DNA damage repair, EMT, autophagy, cancer stem cell characteristics, and metabolic reprogramming. This indicates that NEAT1 may be an important target to overcome chemotherapy resistance and is expected to be a potential biomarker to predict the effect of chemotherapy. This article summarizes the expression characteristics and clinical characteristics of NEAT1 in different cancers, and deeply discusses the regulatory role of NEAT1 in cancer chemotherapy resistance and related molecular mechanisms, aiming to clarify NEAT1 as a new target to overcome cancer chemotherapy resistance and the feasibility of chemotherapy sensitizers, with a view to providing a potential therapeutic direction for overcoming the dilemma of cancer resistance in the future.

The role of lncRNA HCG18 in human diseases.

A substantial number of long noncoding RNAs (lncRNAs) have been identified as potent regulators of human disease. Human leukocyte antigen complex group 18 (HCG18) is a new type of lncRNA that has recently been proven to play an important role in the occurrence and development of various diseases. Studies have found that abnormal expression of HCG18 is closely related to the clinicopathological characteristics of many diseases. More importantly, HCG18 was also found to promote disease progression by affecting a series of cell biological processes. This article mainly discusses the expression characteristics, clinical characteristics, biological effects and related regulatory mechanisms of HCG18 in different human diseases, providing a scientific theoretical basis for its early clinical application.

Tauroursodeoxycholic acid suppresses biliary epithelial cell apoptosis and endoplasmic reticulum stress by miR-107/NCK1 axis in a FXR-dependent manner.

Tauroursodeoxycholic acid (TUDCA) can activate farnesoid X receptor (FXR) to involve in the formation of gallstones. Here, this study aimed to probe the potential mechanism of TUDCA-FXR network in the formation of bile duct stone. The levels of TUDCA, FXR and NCK1 were decreased, while the level of miR-107 was increased in the serum of bile duct stone patients. FXR expression was positively correlated with TUDCA or NCK1 expression in patients, moreover, TUDCA pretreatment in biliary epithelial cells increased the levels of FXR and NCK1, and rescued the decrease of NCK1 caused by FXR knockdown in cells. Then functional analysis showed FXR knockdown caused apoptosis and endoplasmic reticulum stress (ERS) as well as suppressed proliferation in biliary epithelial cells in vitro, which were attenuated by TUDCA pretreatment or NCK1 overexpression Mechanistically, NCK1 was a target of miR-107, which was up-regulated by FXR silencing, and FXR knockdown-induced decrease of NCK1 was rescued by miR-107 inhibition. Additionally, miR-107 expression was negatively correlated with TUDCA expression in bile duct stone patients, and TUDCA pretreatment in biliary epithelial cells decreased miR-107 expression by FXR. Functionally, the pretreatment of TUDCA or FXR agonist suppressed miR-107-evoked apoptosis and ERS in biliary epithelial cells. In conclusion, TUDCA up-regulates FXR expression to activate NCK1 through absorbing miR-107, thus suppressing the apoptosis and ERS in biliary epithelial cells, these results provided a theoretical basis for elucidating the mechanism of bile duct stone formation.

WWP2 overexpression inhibits the antitumor effects of doxorubicin in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common liver cancer that accounts for 90% of cases. Doxorubicin exhibits a broad spectrum of antitumor activity and is one of the most active agents in HCC. WW domain-containing protein 2 (WWP2) is highly expressed in HCC tissues and activates protein kinase B (AKT) signaling pathway to enhance tumor metastasis. However, the role of WWP2 in the glycolysis and antitumor effects of doxorubicin and the epigenetic alterations of WWP2 in HCC remain to be elucidated. The levels of WWP2 and N6-methyladenosine methyltransferase-like 3 (METTL3) in clinical samples and cells were investigated. WWP2 were silenced or overexpressed to study the role of WWP2 in regulating cell proliferation, colony formation, and glycolysis. RNA immunoprecipitation was performed to test m6 A levels. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blot were used to measure mRNA and protein, respectively. WWP2 silencing inhibits cell proliferation, colony formation, and glycolysis, while WWP2 overexpression has the inverse effects via the AKT signaling pathway. Silencing WWP2 enhances doxorubicin's antitumor effect, while WWP2 overexpression suppresses doxorubicin's antitumor effect. Data also support that METTL3 mediates WWP2 m6A modification, and m6A reader, IGF2BP2, binds to the methylated WWP2 to promote the stability of WWP2, leading to upregulation of WWP2. METTL3 mediates WWP2 m6A modification, which can be recognized and bound by IGF2BP2 to increase the stability of WWP2, leading to WWP2 overexpression which inhibits the antitumor effects of doxorubicin through METTL3/WWP2/AKT/glycolysis axis.

Seismic response investigation of prestressed anchor cable supporting rock slope with weak interlayer in Qinghai-Tibet Plateau, China.

Earthquake-induced rock landslides in the eastern mountains of the Tibetan Plateau, especially landslides with weak interlayers pose a significant threat to major construction projects. Prestressed anchor cable is one of the main reinforcement methods of rock slopes. This paper combines shaking table model tests and numerical simulation to study the reinforcement effect and dynamic response characteristics of prestressed anchor cables applied to rock slopes with weak interlayers under strong earthquakes. The research results show that prestressed anchor cables can effectively reinforce slopes with weak interlayers. A small cable inclination, a small spacing and a high prestress are recommended in the seismic reinforcement design of prestressed anchor cable. In addition, the characteristics of slope progressive damage and prestress loss under the earthquake are found by the shaking table test. The results have been applied in hazard prevention and control of rock slopes on the Chengdu-Lanzhou Railway at the eastern Qinghai-Tibet Plateau.

Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: A systematic review and meta-analysis of propensity score-matched studies.

Purpose: Laparoscopic liver resection (LLR) is a widely practiced therapeutic method and holds several advantages over open liver resection (OLR) including less postoperative pain, lower morbidity, and faster recovery. However, the effect of LLR for the treatment of hepatocellular carcinoma (HCC) in elderly patients remains controversial. Therefore, we aimed to perform the first meta-analysis of propensity score-matched (PSM) studies to compare the short- and long-term outcomes of LLR versus OLR for elderly patients with HCC. Methods: Databases including PubMed, Embase, Scopus, and Cochrane Library were systematically searched until April 2022 for eligible studies that compared LLR and OLR for the treatment of HCC in elderly patients. Short-term outcomes include postoperative complications, blood loss, surgical time, and length of hospital stay. Long-term outcomes include overall survival (OS) rate and disease-free survival (DFS) rate at 1, 3, and 5 years. Results: A total of 12 trials involving 1,861 patients (907 in the LLR group, 954 in the OLR group) were included. Compared with OLR, LLR was associated with lower postoperative complications (OR 0.49, 95% CI 0.39 to 0.62, P < 0.00001, I 2 = 0%), less blood loss (MD -285.69, 95% CI -481.72 to -89.65, P = 0.004, I 2 = 96%), and shorter hospital stay (MD -7.88, 95% CI -11.38 to -4.37, P < 0.0001, I 2 = 96%), whereas operation time (MD 17.33, 95% CI -6.17 to 40.83, P = 0.15, I 2 = 92%) was insignificantly different. Furthermore, there were no significant differences for the OS and DFS rates at 1, 3, and 5 years. Conclusions: For elderly patients with HCC, LLR offers better short-term outcomes including a lower incidence of postoperative complications and shorter hospital stays, with comparable long-term outcomes when compared with the open approach. Our results support the implementation of LLR for the treatment of HCC in elderly patients. Systematic review registration: https://inplasy.com/inplasy-2022-4-0156/, identifier INPLASY202240156.

TRESK channel contributes to depolarization-induced shunting inhibition and modulates epileptic seizures.

Glutamatergic and GABAergic synaptic transmission controls excitation and inhibition of postsynaptic neurons, whereas activity of ion channels modulates neuronal intrinsic excitability. However, it is unclear how excessive neuronal excitation affects intrinsic inhibition to regain homeostatic stability under physiological or pathophysiological conditions. Here, we report that a seizure-like sustained depolarization can induce short-term inhibition of hippocampal CA3 neurons via a mechanism of membrane shunting. This depolarization-induced shunting inhibition (DShI) mediates a non-synaptic, but neuronal intrinsic, short-term plasticity that is able to suppress action potential generation and postsynaptic responses by activated ionotropic receptors. We demonstrate that the TRESK channel significantly contributes to DShI. Disruption of DShI by genetic knockout of TRESK exacerbates the sensitivity and severity of epileptic seizures of mice, whereas overexpression of TRESK attenuates seizures. In summary, these results uncover a type of homeostatic intrinsic plasticity and its underlying mechanism. TRESK might represent a therapeutic target for antiepileptic drugs.

Lamc1 promotes the Warburg effect in hepatocellular carcinoma cells by regulating PKM2 expression through AKT pathway.

Hepatocellular carcinoma (HCC), the most common aggressive malignancy of liver, is the third leading cause of cancer death across the world. Laminin gamma 1 (Lamc1), encodes laminin-γ1, an extracellular matrix protein involved in various progresses such as tumor cell proliferation and metabolism. In the present study, high expression of Lamc1 and PKM2 was observed in tumor tissues of HCC patients. In vitro, down-regulation of Lamc1 inhibited proliferation of HCC cells by promoting cell death, reduced glucose consumption and lactate production, accompanied by a decrease in the expression of glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA), and PTEN increased, as well as PTEN S380 and AKT S473/T308 phosphorylation decreased, while Lamc1 up-regulation had the opposite effect. The effects of PKM2 were similar to that of Lamc1 and markedly counteracted the effects of Lamc1 down-regulation. In addition, Lamc1-induced increase in PKM2 expression was strongly attenuated by a PI3K inhibitor, LY294002 or a si-p110 PI3K, with a significant decrease in GLUT1 and LDHA expression, as well as decreased AKT T308 phosphorylation. Thus, we speculated that Lamc1 was implicated in the progression of HCC probably by regulating PKM2 expression through PTEN/AKT pathway.

Ezrin expression in the primary hepatocellular carcinoma patients and associated with clinical, pathological characteristics.

OBJECTIVE: The aim of this study was to assess Ezrin expression in the primary hepatic carcinoma patients and associated with clinical, pathological characteristics. MATERIALS AND METHODS: Fifty-one patients with primary hepatocellular carcinoma (PHC) with completed clinical data were retrospectively analyzed in this study. The Ezrin expression in PHC and normal control liver tissue was tested by immunohistochemical assay. The Ezrin expression and relationship with clinical characteristics were evaluated. RESULTS: The Ezrin positive rate were 66.7% and 15.7% with expression score of 3.21 ± 1.46 and 0.60 ± 1.10, respectively, in the cancer tissue and control tissue with statistical difference (P < 0.05). The Ezrin expression was associated with the metastasis status of the patients (P < 0.05) but not associated with the age (P > 0.05), gender (P > 0.05), differentiation (P > 0.05), and tumor diameter (P > 0.05). CONCLUSION: Ezrin protein is highly expressed in human PHC tissue which can be used for the prediction of metastasis disease.