Silencing long intergenic non-coding RNA 00707 enhances cisplatin sensitivity in cisplatin-resistant non-small-cell lung cancer cells by sponging miR-145.

The aberrant expression of long non-coding RNAs is closely associated with drug resistance in multiple types of cancer. Long intergenic non-coding RNA 00707 (LINC00707) has previously been reported to be an oncogene able to promote lung adenocarcinoma cell proliferation and metastasis. However, its role in the progression of cisplatin (DDP) resistance in non-small-cell lung cancer (NSCLC) requires further elucidation. In the present study, LINC00707 and microRNA (miR)-145 expression levels were measured using reverse transcription-quantitative PCR (RT-qPCR). MTT and flow cytometric assays were performed to evaluate the IC50 value of DDP and cell apoptosis, respectively. Bcl-2, Bax, multidrug resistance protein 1 (MRP1) and P-glycoprotein (P-gp) mRNA and protein expression were detected using RT-qPCR and western blotting, respectively. The interaction between LINC00707 and miR-145 was explored using a luciferase reporter assay. LINC00707 expression was found to be significantly upregulated in DDP-resistant A549 cells (A549/DDP) cells when compared with that in parental A549 cells. LINC00707 knockdown reduced the IC50 value of DDP, enhanced apoptosis and inhibited Bcl-2, MRP1 and P-gp expression, while promoting Bax expression in A549/DDP cells. miR-145 expression was found to be significantly decreased in A549/DDP cells when compared with in A549 cells. LINC00707 directly interacted with miR-145 and negatively regulated its expression. Furthermore, miR-145 downregulation weakened the effect of LINC00707 knockdown in A549/DDP cells. Therefore, silencing of LINC00707 enhanced DDP sensitivity in A549/DDP cells by sponging miR-145, thereby shedding light on LINC00707 and its corresponding molecular mechanisms involved in the progression of DDP resistance in NSCLC cells.

Factors Promoting Tamoxifen Resistance in Breast Cancer via Stimulating Breast Cancer Stem Cell Expansion.

Estrogen receptor-alpha positive (ER(+)) breast cancer constitutes 70-75% of the disease incidence. Tamoxifen has been the basis of endocrine therapy for patients with ER(+) breast cancer for more than three decades. The treatment reduces the annual mortality rate of breast cancer by 31%, and remains the most effective targeted cancer therapy. However, approximately one-third of patients treated with adjuvant tamoxifen suffer from aggressive recurrent disease. Resistance to tamoxifen, thus, remains a major challenge in providing effective treatments for these patients. In an effort to overcome the resistance, intensive research has been conducted to understand the underlying mechanisms; this has resulted in the identification of complex factors/pathways contributing to tamoxifen resistance, including modulations of the ERsignaling, upregulation of a set of growth factor receptor networks (HER2, EGFR, FGFR, and IGF1R), alterations of the PI3K-PTEN/AKT/mTOR pathway, and an elevation of the NF-κB signaling. Despite these advances, our understanding of the acquired resistance remains fragmented and there is a lack of a platform to integrate these diversified molecular factors/ pathways into a cohesive mechanistic model. Nonetheless, at the cellular level, it is becoming increasingly recongnized that cancer stem cells (CSCs) are key in driving cancer metastasis and therapy resistance. Likewise, evidence is emerging for the critical contributions of breast cancer stem cells (BCSCs) to tamoxifen resistance. In this review, we will discuss these recent developments of BCSC-mediated resistance to tamoxifen and the contributions of those demonstrated molecular factors/pathways to BCSC expansion during the emergency of tamoxifen resistance.

[Evaluating the missing heritability of bipolar disorder using the multifactorial liability threshold model].

In order to evaluate the missing heritability of bipolar disorder, we queried the GWAS catalog of National Human Genome Research Institute, retrieve all the susceptible gene variation of bipolar disorder, and calculate the heritability explanation degree of each susceptibility variant using the multifactorial liability threshold model. The total heritability explanation degree of bipolar disorder was obtained through summing up the heritability explanation degree of each susceptibility variant. Then, we evaluated the missing heritability of bipolar disorder based on the total heritability explanation degree. The results showed that the total heritability explanation degree of bipolar disorder explained by known susceptible variants was 38.34%, and the other 61.66% of heritability can't be explained by known susceptibility variants, which belong to the missing heritability of bipolar disorder. The total heritability explanation degree of bipolar disorder in this study was significantly increased compared to earlier similar studies abroad. With constant discovery of new bipolar disorder susceptibility variants, the missing heritability of bipolar disorder has been greatly reduced, but the missing heritability of bipolar disorder still exists and occupies a large part of the bipolar disorder heritability, indicating that the molecular genetic mechanisms of bipolar disorder need to be further clarified.

[Expression of hepatocyte growth factor and its receptor in gastric cancer].

OBJECTIVE: To investigate the role of expression of hepatocyte growth factor (HGF) and its receptor (c-Met) in gastric cancer. METHODS: The expression of HGF and c-Met was detected with SABC immunohistochemistry in 44 specimens of gastric cancer, 20 chronic superficial gastritis, 10 chronic atrophic gastritis and 16 gastric ulcer tissues. RESULTS: No positive expression of HGF/c-Met was found in the chronic superficial gastritis specimens. The positivity rates of HGF in the gastric cancer was 72.7% (32/44), significantly higher than that in chronic atrophic gastritis [20% (2/10), P<0.005] and gastric ulcer [37.5% (6/16). P<0.025]. The positivity rates of c-Met in gastric cancer [77.3% (34/44)] was also significantly higher than that in chronic atrophic gastritis [40% (4/10), P<0.05] and gastric ulcer [37.5% (6/16), P<0.025]. CONCLUSION: Co-expression of HGF and c-Met in gastric cancer may promote the progression of the malignancy, and also opens a new pathway for the therapy of gastric cancer.

[The influence of platelets on PTA1 expression and PDGF release from ECV304 cells].

AIM: To study the influence of platelets on the expression of platelet/T cell activation antegen 1 (PTA1) and release of platelet-derived growth factor (PDGF) from vascular endothelial cells (ECV304) stimulated with pregnancy induced hypertention (PIH) patient sera. METHODS: The expression of PTA1 on ECV304 cells stimulated with PIH patient sera and incubated with or without platelets was analyzed by flow cytometry. ELISA was employed to measure the quantity of PDGF released from ECV304 cells. RESULTS: After incubation with platelets, PTA1 expression on ECV304 cells stimulated with PIH patient sera decreased. PIH sera induced more PDGF release from ECV304 cells than sera from normal pregnant women. Coculture with platelets increased PDGF release from ECV304 stimulated with PIH patient sera. CONCLUSION: PTA1 molecule may mediate the adhesion between ECV304 cells and platelets, which lead to the release of PDGF.

Elemental contents in serum of pregnant women with gestational diabetes mellitus.

Diabetes mellitus is characterized by hyperglycemia and is closely related to trace elements. Quite a few pregnant women suffer from impaired glucose tolerance (IGT) or gestational diabetes mellitus (GDM). Investigation of the changes of elemental contents in serum of the pregnant women with IGT and GDM is significant in the etiological research and cure of the diseases. In the present work, the elements Cu, Zn, Ca, Sr, Mg, P, Fe, and Al in the serum of pregnant women were determined. The elemental contents in different experimental groups were compared. Also, the correlation between elemental contents and gestational period was observed. The results showed that compared with normal pregnant women, the Cu contents in serum of pregnant women with GDM increased, but Zn contents had a decreasing trend. In addition, for all pregnant women, the Ca contents in serum had an obvious inverse correlation with gestational period.

Cryopreservation and xenotransplantation studies of microencapsulated rat pancreatic islets.

Islets of Langerhans were isolated from the Sprague Dawley rat pancreas digested by injected collagenase, and purified by Ficoll density gradient centrifugation. In order to make smaller and more uniform microencapsulated islets, we designed a special high-voltage electrostatic microcapsule generator. The effects of operational parameters of the generator on the size and the uniformity of microcapsules were analyzed, such as the voltage, the plunger speed of suspension delivery to the needle tip, the distance between needle tip and solution surface. The optimal parameter combinations for making microcapsules are: 5 kV of voltage, 50 mm/h of the plunger speed, and 20 mm distance. The high-voltage electric system can produce uniform microcapsules with diameters ranging from 0.3 to approximately 0.5 mm, which are smaller and more uniform than those produced by air-jet system. A comparison of the cryopreservation effects between microencapsulated islets and unencapsulated islets showed that the microcapsules can protect the fragile islets from freezing damage, and increase the retrieval rate from 68.5% to 92.6%. Xenotransplantation of the cryopreserved rat islets resulted in the normalization of the metabolic blood glucose of the diabetic mice for 90 days, whereas the unencapsulated islets were easily fragmented and lost during the freezing process. They only reversed hyperglycemia for less than 3-5 days.