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.

Long non-coding RNA FEZF1-AS1 promotes rectal cancer progression by competitively binding miR-632 with FAM83A.

The long non-coding RNA (lncRNA) forebrain embryonic zinc finger protein 1 antisense RNA1 (FEZF1-AS1) was recently identified as an oncogenic gene in several types of tumors. The biological function of FEZF1-AS1 in rectal cancer progression, however, remains unknown. In the present study, we discover that FEZF1-AS1 is significantly upregulated in rectal cancer tissues and cells. Knocking down of FEZF1-AS1 suppresses cell proliferation, migration, and invasion , and tumorigenesis . Furthermore, FEZF1-AS1 functions as a competing endogenous RNA (ceRNA) for miR-632, resulting in the suppression of family with sequence similarity 83, member A (FAM83A). Overall, our findings reveal that FEZF1-AS1/miR-632/FAM83A axis plays an oncogenic role in rectal cancer progression, suggesting that it may be a novel therapeutic target for rectal cancer.

lncRNA ITGB8-AS1 functions as a ceRNA to promote colorectal cancer growth and migration through integrin-mediated focal adhesion signaling.

Long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis and progression of colorectal cancer (CRC). However, functions of most lncRNAs in CRC and their molecular mechanisms remain uncharacterized. Here we found that lncRNA ITGB8-AS1 was highly expressed in CRC. Knockdown of ITGB8-AS1 suppressed cell proliferation, colony formation, and tumor growth in CRC, suggesting oncogenic roles of ITGB8-AS1. Transcriptomic analysis followed by KEGG analysis revealed that focal adhesion signaling was the most significantly enriched pathway for genes positively regulated by ITGB8-AS1. Consistently, knockdown of ITGB8-AS1 attenuated the phosphorylation of SRC, ERK, and p38 MAPK. Mechanistically, ITGB8-AS1 could sponge miR-33b-5p and let-7c-5p/let-7d-5p to regulate the expression of integrin family genes ITGA3 and ITGB3, respectively, in the cytosol of cells. Targeting ITGB8-AS1 using antisense oligonucleotide (ASO) markedly reduced cell proliferation and tumor growth in CRC, indicating the therapeutic potential of ITGB8-AS1 in CRC. Furthermore, ITGB8-AS1 was easily detected in plasma of CRC patients, which was positively correlated with differentiation and TNM stage, as well as plasma levels of ITGA3 and ITGB3. In conclusion, ITGB8-AS1 functions as a competing endogenous RNA (ceRNA) to regulate cell proliferation and tumor growth of CRC via regulating focal adhesion signaling. Targeting ITGB8-AS1 is effective in suppressing CRC cell growth and tumor growth. Elevated plasma levels of ITGB8-AS1 were detected in advanced-stage CRC. Thus, ITGB8-AS1 could serve as a potential therapeutic target and circulating biomarker in CRC.

Mechanism of heparin interference in detection of LIAISON® Rubella IgM.

AIMS: To investigate the effects of heparin in detection of LIAISON® Rubella IgM (Rub-M) and the mechanism of interference. METHODS: Different concentrations of lithium heparin and sodium heparin were added to ten serum samples. The relative light units (RLU) value of Rub-M was measured using the LIAISON XL detection system. Different levels of IgM serum were incubated with magnetic particle in Rub-M detection kit at 4 °C for 4 h, blocking anti-human IgM-specific antibodies coated on the surface of magnetic particle. Separately, the rubella virus antigen in Rub-M detection kit was replaced by phosphate-buffered saline (PBS). The RLU values of LIAISON® Rub-M of original serum and serum containing various concentrations of heparin were measured after the above two different treatments. RESULTS: The RLU value of LIAISON® Rub-M increased with the increase of heparin content lower than 40 IU/mL, and reached a peak value at 40-50 IU/mL. The RLU value of LIAISON® Rub-M then decreased with the decrease of heparin concentration. When rubella virus antigen was replaced by PBS, the RLU value of LIAISON® Rub-M of serum samples containing 40 IU/mL heparin decreased significantly. The blocking concentration of IgM increased gradually, and the RLU value of LIAISON® Rub-M of seven serum samples containing 40 IU/mL heparin also decreased gradually. CONCLUSION: Plasma with heparin cannot be used to the detection of LIAISON® Rub-M. Heparin may participate in the reaction by binding with rubella virus antigen and anti-human IgM-specific antibodies coated on the surface of magnetic particle, thus affecting the detection results.

circFBXL5 promotes breast cancer progression by sponging miR-660.

Increasing studies have revealed that circular RNAs (circRNAs) play important roles in cancer progression. However, the potential involvement of circRNAs in breast cancer metastasis to lung is not clear so far. In this study, we conducted circular RNA microarrays of primary breast cancer tissues and lung metastatic tissues. The results revealed that circFBXL5 (hsa_circ_0125597) up-regulated the most in lung metastatic tissues. Survival analysis revealed that high levels of circFBXL5 correlated with worse outcome of breast cancer. Further experiments showed that knockdown of circFBXL5 inhibited breast cancer cell proliferation and migration to lung. Mechanism study showed that circFBXL5 acted as a sponge for miR-660 and compete binding to miR-660 with SRSF6, leading to increased expression of SRSF6. Collectively, our study highlighted the regulatory function of the circFBXL5/miR-660/SRSF6 pathway in breast cancer progression, which could be potential therapeutic targets for breast cancer.

Bilateral Extradural Posterior Inferior Cerebellar Artery Origins Where Vertebral Artery Ascends Between Transverse Foramina of C-2 and C-1, with Simultaneous Right Double Origin PICA: Rare Case Report and Literature Review.

BACKGROUND: The location of the origin of the posterior inferior cerebellar artery (PICA) is highly variable. An extracranial origin PICA from the vertebral artery (VA) is not rare. But the PICA originated extradurally where the VA ascends between the transverse foramina of C-2 and C-1, a rare anatomic variant. Double-origin PICA is another rare anatomic variant observed in 1%-4% of patients in whom 2 PICA branches converge distally. CASE DESCRIPTION: We present a rare cadaveric anatomy case in which both PICAs originated extradurally between the vertebrae C1 and C2, a simultaneously existing right double-origin PICA. For this case, the right PICA was a double-origin PICA, including 1 extradural origin in which the VA ascends between the transverse foramina of C-2 and C-1 and another being intradural and intracranial. CONCLUSIONS: To our knowledge, this is the first report of a cadaveric anatomy case of bilateral PICA that originated extradurally between the vertebrae C-1 and C-2, and simultaneously there existed a right double-origin PICA. Such a case is rare, but understanding of the anatomic variation is important. To avoid complications during surgery at the craniovertebral junction, these potential variations should be correctly identified preoperatively.

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.