Estrogen-Induced LncRNA, LINC02568, Promotes Estrogen Receptor-Positive Breast Cancer Development and Drug Resistance Through Both In Trans and In Cis Mechanisms.

Endocrine therapy is the frontline treatment for estrogen receptor (ER) positive breast cancer patients. However, the primary and acquired resistance to endocrine therapy drugs remain as a major challenge in the clinic. Here, this work identifies an estrogen-induced lncRNA, LINC02568, which is highly expressed in ER-positive breast cancer and functional important in cell growth in vitro and tumorigenesis in vivo as well as endocrine therapy drug resistance. Mechanically, this work demonstrates that LINC02568 regulates estrogen/ERα-induced gene transcriptional activation in trans by stabilizing ESR1 mRNA through sponging miR-1233-5p in the cytoplasm. Meanwhile, LINC02568 contributes to tumor-specific pH homeostasis by regulating carbonic anhydrase CA12 in cis in the nucleus. The dual functions of LINC02568 together contribute to breast cancer cell growth and tumorigenesis as well as endocrine therapy drug resistance. Antisense oligonucleotides (ASO) targeting LINC02568 significantly inhibits ER-positive breast cancer cell growth in vitro and tumorigenesis in vivo. Furthermore, combination treatment with ASO targeting LINC02568 and endocrine therapy drugs or CA12 inhibitor U-104 exhibits synergistic effects on tumor growth. Taken together, the findings reveal the dual mechanisms of LINC02568 in regulating ERα signaling and pH homeostasis in ER-positive breast cancer, and indicated that targeting LINC02568 might represent a potential therapeutic avenue in the clinic.

LncRNA LUCRC Regulates Colorectal Cancer Cell Growth and Tumorigenesis by Targeting Endoplasmic Reticulum Stress Response.

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide, and is well known for its strong invasiveness, rapid recurrence, and poor prognosis. Long non-coding RNAs (lncRNAs) have been shown to be involved in the development of various types of cancers, including colorectal cancer. Here, through transcriptomic analysis and functional screening, we reported that lncRNA LUCRC (LncRNA Upregulated in Colorectal Cancer) is highly expressed in colorectal tumor samples and is required for colorectal cancer cell proliferation, migration, and invasion in cultured cells and tumorigenesis in xenografts. LUCRC was found to regulate target gene expression of unfolded protein response (UPR) in endoplasmic reticulum (ER), such as BIP. The clinical significance of LUCRC is underscored by the specific presence of LUCRC in blood plasma of patients with colorectal cancers. These findings revealed a critical regulator of colorectal cancer development, which might serve as a therapeutic target in colorectal cancer.

[Cost-benefit analysis on the strategy of social health insurance regarding vaccination against influenza in Xi'an city].

OBJECTIVE: To assess the economic implications of an annual vaccination strategy against influenza among people who were on a social-health program. METHODS: A retrospective cohort study was conducted. 1900 persons who had received the influenza vaccine were served as vaccine group, while 1049 persons who did not receive the vaccine were served as controls. Cluster random sampling method was used. Both of these two groups came from Donfang Company in which there were 12,109 employers in total and all of them joined the social health insurance program. The survey was carried out when the influenza vaccine was given one year ago. RESULTS: The rates of vaccine group and control group for respiratory system diseases and cardiovascular diseases who were hospitalized, were 0.51%, 2.47% and 1.64%, 5.62% which showed 68.90% and 56.05% decrease, when compared with the control group. The crude inpatient rate among vaccinees and control group after receiving the vaccination for three and four month were 0.62%, 0.80% and 0.28%, 1.00% respectively. The inpatient rate of oldest-age group decreased by 53.59%, compared with control group. The cost-benefit ratio generated by the use of influenza vaccine in reducing the hospitalization rate was 6.48:1 for Social Health Insurants in Xi'an city. CONCLUSION: The Strategy to vaccinate the social-health-insured residents on influenza in Xi'an city had gained better economic benefits in reducing the hospitalization rate of respiratory system diseases and cardiovascular diseases for mild and old-aged persons.

[Detection of the frequencies of numerical and structural chromosome aberrations in sperm of benzene series-exposed workers by multi-color fluorescence in situ hybridization].

To study the frequencies of numerical and structural aberrations for chromosome in sperm of benzene exposed workers, the multi-color FISH was used. Four DNA probes(one for chromosome 1 centromere and one for 1 p terminal, and two for chromosome 18 centromere) were hybridized with interphase sperms, and the frequencies of numerical aberrations for chromosome 1, 18 and structural aberrations of chromosome 1 were detected simultaneously. The time weighted average concentration (TWA) of benzene in workplace (42.29 mg/m3) was higher than that of our national maximum allowable concentration (6 mg/m3). The geometric concentration of urinary trans, trans-muconic acid(tt-MA) in exposed group was significantly higher than that of control group. A total of 144,282 sperm of 15 benzene-exposed workers and 135,937 sperm in 14 controls were scored. The frequency of hybridization efficiency was 99.85%. The mean frequencies of disomic sperms for chromosome 1 and 18 in exposed group(0.088% +/- 0.041%, and 0.087% +/- 0.049%, respectively) were statistically increased over that of the control group(0.045% +/- 0.024%, and 0.035% +/- 0.028%), and the mean frequencies of nullisomic sperms for chromosome 1 and 18(0.11% +/- 0.059%, 0.075% +/- 0.035%) in exposed group were statistically increased over that of control group too (0.048% +/- 0.018%; 0.045% +/- 0.024%). The frequencies of diploidy sperm were no difference in both exposed and control groups. The mean frequencies of terminal duplication and terminal deletion for chromosome 1 p(0.16% +/- 0.037%; 0.14% +/- 0.053%, respectively) were significantly increased over that of control group(0.082% +/- 0.023%; 0.069% +/- 0.028%, respectively). The mean frequencies of centromeric duplication and centromeric deletion for chromosome 1(0.10% +/- 0.035%; 0.10% +/- 0.041%, respectively) were significantly increased over that of control group(0.075% +/- 0.023%; 0.060% +/- 0.029%). Our experiments showed that exposed to benzene at higher concentration(42.29 mg/m3) may induce increases in frequencies not only of numerical aberrations for chromosome 1 and 18, but also of structural aberrations for chromosome 1 of sperms in exposed workers.

[Detection of DNA damage induced by carbon disulfide in mice sperm with single-cell gel electrophoresis assay].

OBJECTIVE: To study the genotoxicity of carbon disulfide by detecting DNA damage in mice sperm with single-cell gel electrophoresis assay (SCGE). METHODS: SCGE was used to detect sperm DNA damage. The index of DNA damage, tail length and tail moment were used to evaluate the extent of DNA damage. RESULTS: In three dosage groups, the rate of DNA damage (67.14%, 84.29% and 91.00%, respectively), index of DNA damage intensity (507, 656 and 745, respectively), tail length (5.87, 8.81 and 13.49 microm, respectively) and tail moment (1.30, 1.63, 2.66 microm, respectively) were significantly increased, while the percentage of head of the comet was significantly decreased (84.55%, 73.84% and 55.71%, respectively). A significant changes were clearly observed in all dosage groups compared to those of the control group (P<0.05). CONCLUSION: SCGE which is a quick and sensitive method to detect DNA damage induced by CS2 may be used to monitor carcinogen and mutagen.