Nuclear lncRNA HOXD-AS1 suppresses colorectal carcinoma growth and metastasis via inhibiting HOXD3-induced integrin ß3 transcriptional activating and MAPK/AKT signalling.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been indicated to play critical roles in cancer development and progression. LncRNA HOXD cluster antisense RNA1 (HOXD-AS1) has recently been found to be dysregulated in several cancers. However, the expression levels, cellular localization, precise function and mechanism of HOXD-AS1 in colorectal carcinoma (CRC) are largely unknown. METHODS: Real-time PCR and in situ hybridization were used to detect the expression of HOXD-AS1 in CRC tissue samples and cell lines. Gain- and loss-of-function experiments were performed to investigate the biological roles of HOXD-AS1 in CRC cell line. RNA pull down, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to investigate the mechanisms underlying the functions of HOXD-AS1 in CRC. RESULTS: We observed that HOXD-AS1 was located in the nucleus of CRC cells and that nuclear HOXD-AS1 was downregulated in most CRC specimens and cell lines. Lower levels of nuclear HOXD-AS1 expression were associated with poor outcomes of CRC patients. HOXD-AS1 downregulation enhanced proliferation and migration of CRC cells in vitro and facilitated CRC tumourigenesis and metastasis in vivo. Mechanistic investigations revealed that HOXD-AS1 could suppress HOXD3 transcription by recruiting PRC2 to induce the accumulation of the repressive marker H3K27me3 at the HOXD3 promoter. Subsequently, HOXD3, as a transcriptional activator, promoted Integrin ß3 transcription, thereby activating the MAPK/AKT signalling pathways. CONCLUSION: Our results reveal a previously unrecognized HOXD-AS1-HOXD3-Integrin ß3 regulatory axis involving in epigenetic and transcriptional regulation constitutes to CRC carcinogenesis and progression.

[Stromal cell-derived factor-1 inducing metastasis squamous cell carcinoma of head and neck induced via integrin ανß3-CXC chemokine receptor 4/7 biological axis].

OBJECTIVE: To observe the influence of LM609/AMD3100/CCX754 on chemotactic capability, cytoskeleton, and expression of integrin ανß3 protein of squamous cell carcinoma of head and neck (SCCHN) cell line PCI-13 induced by stromal cell-derived factor-1 (SDF-1) in vitro. METHODS: Migration assays, flow cytometry and immunofluorescence were used to observe the effects of SDF-1, LM609, AMD3100 and CCX754 on the migration, cytoskeleton and the expression of integrin ανß3 protein in PCI-13 cell lines. RESULTS: SDF-1 favored PCI-13 cell migration, pseudopod formation, and activities of integrin ανß3 phosphorylation. LM609, AMD3100, and CCX754 blocked all these effects. CONCLUSIONS: SDF-1 can induce metastatic SCCHN by integrin ανß3-CXC chemokine receptor (CXCR) 4/CXCR7 axi. LM609, AMD3100, and CCX754 and can reduce the regulation of SDF-1 on SCCHN activity.

[Systematic retrospective study of oral cancer-related quality of life scale].

OBJECTIVE: The quality of life (QOL) related to oral cancer has recently become a focus of clinical studies. This study aims to systematically review the current research situation of QOL of local and foreign oral cancer patients and explore the existing related problems and future research directions to provide references and solutions. METHODS: Through relevant key words, PubMed, Wiley InterScience, Science Direct, CNKI, and Wanfang databases were first searched. The related target literature from 2000 to 2017 were screened. Finally, the frequency of oral cancer related to QOL scale used in literature was calculated, and the related scales were briefly introduced. RESULTS: From the target literature, 218 English target literature, 55 Chinese target literature, 24 English scales, and 12 Chinese scales were selected. The most widely used scales for assessing the QOL of patients with oral cancer were as follows: University of Washington Quality of Life Questionnaire (UW-QOL), European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30/Head and Neck 35 (EORTC QLQ-C30/H&N35), 36-Item Short-Form Health Survey (SF-36), Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N), and Oral Health Impact Profile (OHIP). CONCLUSIONS: The QOL related to oral cancer was well underway, and the study of geographical distribution was widespread. However, the work on self-developed scale remains inadequate. UW-QOL, EORTC QLQ-C30/H&N35, and FACT-H&N can be utilized as the preferred scales for evaluating the QOL of oral cancer patients. A specific disease-related function scale can also be selected according to specific research objectives.

[Influencing factors on the quality of life and medical coping style of patients with oral cancer].

OBJECTIVE: To evaluate the influencing factors on the postoperative quality of life and to analyze the coping styles of patients with oral cancer. METHODS: A total of 131 oral cancer cases confirmed through diagnostic criteria were investigated to analyze the influencing factors on the quality of life (QOL) and the relationship between coping style and QOL of these patients by using the fourth edition of the University of Washington Quality of Life Questionnaire (UWQOL) and medical coping modes questionnaires (MCMQ), respectively. RESULTS: Among the 131 questionnaires collected, only 126 were valid with a recovery rate of 96.18% (126/131). Single factor analysis showed that age, marital status, educational level, other systemic diseases, personal income level, tooth loss, operation times, adjuvant radiotherapy, cancer staging, cervical lymph node dissection, recurrence, and jaw resection yielded different UWQOL scale scores (P<0.05). Multiple regression analysis showed that the loss of teeth, cancer staging, recurrence, and jaw resection yielded statistically significant differences in the total score of UWQOL (P<0.05). Among the coping styles, the average scores of  "confrontation", "avoidance", and "yielding" were 17.54±4.97, 17.79±2.19, and 12.97±5.70, respectively. Compared with the norm, the difference was statistically significant (P<0.05). Correlation analysis showed that "confrontation" and "avoidance" were positively correlated, whereas "yielding" was negatively correlated to QOL (P<0.05). CONCLUSIONS: Age, marital status, educational level, other systemic diseases, personal income level, tooth loss, operation times, adjuvant radiotherapy, cancer staging, cervical lymph node dissection, recurrence, and jaw resection have different effects on the quality of QOL. Tooth loss, cancer staging, recurrence, and jaw resection are the main causative factors affecting the patients' perceived QOL. Personalized treatment and nursing care should be strengthened to improve the coping style and quality of life of patients.

[Use of Zhengzhou University-quality of life scale in 218 postoperative patients with oral cancer].

PURPOSE: The purpose of this study was to explore the best threshold of Zhengzhou University-quality of life(ZZU-QOL) scale in patients with oral cancer 3 to 6 months after operation. METHODS: A questionnaire survey was conducted on 218 patients with oral cancer who met the inclusion criteria. The patients were asked to fill in the ZZU-QOL and the University of Washington Quality of Life Scale(UWQOL). A total of 178 valid questionnaires were collected and the recovery rate was 81.65%. The UWQOL was used as "the gold standard", and the receiver operating characteristic curve (ROC) was drawn to determine the optimal threshold of quality of life scale of Zhengzhou University. Statistical analysis was performed by using SPSS 20 software package. RESULTS: There was a moderate positive correlation between total score of quality of life scale of Zhengzhou University and the total score of the UWQOL (r=0.685, P<0.05). When the ZZU-QOL threshold was 55.682, ROC curve was closest to the upper left corner, its sensitivity and specificity, false negative rate, false positive rate and Youden index were 0.797, 0.676, 0.203, 0.324 and 0.473, respectively. The area under the ROC curve was 0.809, the standard error of the area was 0.047, the 95% confidence interval was 0.718 - 0.901, and the threshold was 56 when the integer was taken. CONCLUSIONS: The optimal threshold of ZZU-QOL in oral cancer patients 3 to 6 months after operation was 56 points, which may be used as the theoretical guidance and basis for evaluation and screening of postoperative quality of life in patients with oral cancer.

[Study of psychological distress and quality of life in patients with oral cancer].

PURPOSE: To explore the relationship between the status quo and influencial factors of oral cancer patients and their quality of life. METHODS: Using the Distress Themometer (DT) and the University of Washington Quality of Life Questionnaire (UW-QOL), 250 patients admitted to the First Affiliated Hospital of Zhengzhou University from October 2016 to September 2017 with oral cancer were investigated. Chi-square test, t test, logistic regression analysis and Spearman correlation analysis were used to analyze the data with SPSS20.0 software package. RESULTS: A total of 250 questionnaires were issued, 239 valid questionnaires were available for analysis. In 239 oral cancer patients, 139 (58.2%) had DT score ≥4. The average total score of UWQOL scale was 53.3±17.1, score <4 was noted in 100 patients (41.8%); the average UWQOL scale was 52.8±17.4. Univariate analysis showed that psychological distress was related to age, educational level, income level, pathological stage, jaw resection and recurrence (χ2 values were 5.12,21.31,34.2,10.69,31.3 and 7.84, respectively, P<0.05 ). Logistic regression analysis showed that age, jaw resection and relapse were the risk factors of psychological distress in patients with oral cancer (OR=4.06, 5.12 and 5.79, respectively; P<0.05). Spearman correlation analysis showed that the scores of pain, recreation, emotion and anxiety in UWQOL scale were negatively correlated with psychological distress scores (r=-0.58, -0.84, -0.66 and -0.69, respectively; P<0.05). CONCLUSIONS: Oral cancer patients have a higher incidence of psychological distress. Younger patients,and those with maxillectomy and recurrence have more serious symptoms of distress.

Chinoketides A and B, Two New Antimicrobial Polyketides from the Endophytes of Distylium chinense with the “Black-Box” Co-culture Method

Two new polyketides, chinoketides A and B (1 – 2) with a known compound xylarphthalide A (3), were isolated from the solid medium of the endophytes from the leaves of the relic plant Distylium chinense with the “black-box” co-culture method, and the structures of two new compounds were elucidated by NMR, MS and CD spectra. And the absolute configurations of chinoketides A (1) and B (2) were determined as 2R,3R,8S and 5R,6S by calculating their ECD spectra to compare with the experimental CD spectra. Finally, the antimicrobial activities were evaluated to Erwinia carotovora sub sp. Carotovora (Jones) Bersey et al, and the results showed that compounds 1 – 3 displayed the antimicrobial activities with MIC value at 20.5, 30.4 and 10.2 µg/mL.

[Development of a quality of life instrument for evaluation of the quality of life scale for Chinese patients with oral cancer].

PURPOSE: To develop a quality of life instrument for Chinese patients with oral cancer and to assess its reliability, validity and sensitivity. METHODS: A 44-item QOL questionnaire was developed with reference to the 36-item medical outcomes study on short-form health status (SF-36) and University of Washington Quality of Life Questionnaire (UW-QOL), combining with China's population and socio-cultural characteristics, named as Zhengzhou university oral cancer quality of life (ZZU-QOL) scale. Based on 271 patients, student's t test, correlation analysis, factor analysis were performed for its reliability and validity using SPSS 19.0 software package. RESULTS: Test-retest reliability: in all areas and for total score between 2 measurements of the correlation coefficient in the range of 0.86-1.00, there was no significant difference. Homogeneity reliability: Cornbrash'a coefficient in all fields was larger than 0.6, indicating the scale had good reliability. Construct validity: ZZU-QOL, SF-36 analysis and UW-QOL scale factor selected by the first seven cumulative contribution factor variance were 69.3%, 63.4% and 66.5%. The criterion validity with SF-36 and UW-QOL was 0.768 and 0.634, respectively. The ZZU-QOL scale can sensitively distinguish differences in preoperative and postoperative quality of life of oral cancer. CONCLUSIONS: The ZZU-QOL scale is practical, reliable and valid, and might be used for measuring the quality of life in Chinese patients with oral cancer.

[Expressions of short palate, lung and nasal epithelium clone 1 in different human tissues].

OBJECTIVE: To examine the expression patterns of short palate, lung and nasal epithelium clone 1 (SPLUNC1) gene in human tissues. METHODS: In situ hybridization was used to detect the expression of SPLUNC1 gene in 37 different human tissues. RESULTS: We found that SPLUNC1 gene was not expressed in squamous epithelial cells of the palate, epidermis, esophagus, or the esophagus-cardia junction, metaplastic squamous cells in the nasopharynx, trachea, or uterus cervix, or tumor cells of esophageal squamous cell carcinoma or lung squamous cell carcinoma. SPLUNC1 gene was not expressed in the single layer columnar epithelia cells in the stomach, gallbladder, jejunum, colon, endometrium, or uterus cervix. SPLUNC1 expression was detected mainly in pseudostratified columnar epithelial cells in the nasopharynx, trachea and bronchi, and was gradually down-regulated from the upper to lower end of the respiratory tract, but was not detected in the lung tissues. SPLUNC1 expression was detected not only in the duct and serous gland cells in the parotid and submandibular glands, but also in cells of submucosal serous glands in the nasopharynx and lung, but not in the cells of the mucosal glands. The parietal cells of the gastric submucosa and epithelial cells of the lobula and ducts of the mammary glands expressed SPLUNC1. The adenocarcinoma cells in the lung, stomach, colon, mammary gland, uterus endometrium and cervix showed strong expressions of SPLUNC1 gene. CONCLUSION: SPLUNC1 expression is highly cell-specific in association with the cell functions.

Inhibition of G protein-coupled receptor 81 (GPR81) protects against ischemic brain injury.

AIM: Lactates accumulate in ischemic brains. G protein-coupled receptor 81 (GPR81) is an endogenous receptor for lactate. We aimed to explore whether lactate is involved in ischemic injury via activating GPR81. METHODS: N2A cells were transfected with GFP-GPR81 plasmids 24 h previously, and then treated with GPR81 antagonist 3-hydroxy-butyrate (3-OBA) alone or cotreated with agonists lactate or 3, 5-dihydroxybenzoic acid (3, 5-DHBA) during 3 h of oxygen-glucose deprivation (OGD). Adult male C57BL/6J mice and primary cultured cortical neurons were treated with 3-OBA at the onset of middle cerebral artery occlusion (MCAO) or OGD, respectively. RESULTS: The GPR81 overexpression increased the cell vulnerability to ischemic injury. And GPR81 antagonism by 3-OBA significantly prevented cell death and brain injury after OGD and MCAO, respectively. Furthermore, inhibition of GPR81 reversed ischemia-induced apoptosis and extracellular signal-regulated kinase (ERK) signaling may be involved in the neuroprotection. CONCLUSIONS: G protein-coupled receptor 81 (GPR81) inhibition attenuated ischemic neuronal death. Lactate may aggravate ischemic brain injury by activating GPR81. GPR81 antagonism might be a novel therapeutic strategy for the treatment of cerebral ischemia.

microRNA-182 targets special AT-rich sequence-binding protein 2 to promote colorectal cancer proliferation and metastasis.

BACKGROUND: Increasing evidence has revealed that microRNAs (miRNA) played a pivotal role in regulating cancer cell proliferation and metastasis. The deregulation of miR-182 has been identified in colorectal cancer (CRC). However, the role and mechanism of miR-182 in CRC have not been completely understood yet. METHODS: The expression levels of miR-182 in CRC tissues and CRC cell lines were examined by performing stem-loop quantitative RT-PCR. The stable over-expression miR-182 cell lines and control cell lines were constructed by lentivirus infection. Subsequently, CCK-8 assay, plate colony formation assay, cell migration, invasion assay and experimental animal models were performed to detect the biological functions of miR-182 in vitro and in vivo. A luciferase reporter assay was conducted to confirm target associations. Western blot and immunohistochemical analysis were performed to examine the expression changes of molecular markers that are regulated by miR-182. RESULTS: We found that miR-182 expression is increased in CRC cells that originated from metastatic foci and human primary CRC tissues with lymph node metastases. The ectopic expression of miR-182 enhanced cell proliferation, invasion, and migration in vitro. Stable overexpression of miR-182 also facilitated tumor growth and metastasis in vivo too. Further research showed that miR-182 could directly target the 3'untranslated region (3'UTR) of SATB2 mRNA and subsequently repress both the mRNA and protein expressions of SATB2, which we identified in previous studies as a CRC metastasis-associated protein. Restoring SATB2 expression could reverse the effects of miR-182 on CRC cell proliferation and migration. Investigations of possible mechanisms underlying these behaviors induced by miR-182 revealed that miR-182 induced epithelial-mesenchymal transition (EMT) by modulating the expression of key cellular molecules in EMT. CONCLUSIONS: Our results illustrated that the up-regulation of miR-182 played a pivotal role in CRC tumorigenesis and metastasis, which suggesting a potential implication of miR-182 in the molecular therapy for CRC.

Free fibula flap: assessment of quality of life of patients with head and neck cancer who have had defects reconstructed.

This study investigated the quality of life (QoL) of patients with head and neck cancer undergoing immediate reconstruction of the mandible with free fibula flap. From March 2006 to January 2011, the QoL of 42 patients was assessed using the Medical Outcomes Study Short Form 36 and the University of Washington QoL (version 4) questionnaires. The assessments were performed at least 24 months after surgery. A total of 31 of the 42 questionnaires (73.8%) were returned. The length of harvested fibula varied from 17.5 to 26.1 cm. In the Short Form 36, the lowest-scoring domain was vitality, whereas the highest scores occurred in physical role. According to the University of Washington QoL, the key domains affected by surgery are chewing, speech, and appearance. The domain of pain has the best score. There was a significant effect on the QoL of patients with head and neck cancer with resections of the mandible who had undergone free fibula flap reconstruction. Data from this study may provide useful information for physicians and patients, which may be of value during discussion of treatment modalities for head and neck cancers.

Quality of life in patients younger than 40 years treated for anterior tongue squamous cell carcinoma.

This study investigated the quality of life in patients younger than 40 years with tongue squamous cell carcinoma. We used the University of Washington Head and Neck Quality of Life scale to compare the quality of life outcomes between young and old patients. Cases were patients younger than 40 years who were treated for anterior tongue squamous cell carcinoma. Controls were patients older than 40 years who were matched to the cases regarding diagnosis, sex, and TNM classification. Two controls were matched for each case; thus, 21 cases and 42 controls were selected. Twenty-one of 33 questionnaires (63.6%) were returned. The median follow-up duration was 3.7 years (range, 1-12 y). In the group of young patients, the best-scoring domains were pain, chewing, and swallowing, whereas the lowest scores were for appearance, mood, and anxiety. Young patients (40 years or younger) reported better function, notably regarding activity, recreation, shoulder, taste, and saliva compared with the old patients with anterior tongue squamous cell carcinoma. The patients younger than 40 years tend to have a good quality of life. Most of them were not significantly affected by pain. Quality of life should be used as part of our treatment of anterior tongue squamous cell carcinoma.

[Assessment of quality of life of oral cancer patients after reconstruction with radial forearm free flaps].

OBJECTIVE: To evaluate the quality of life in patients who had resection of oral cancer and reconstruction by radial forearm free flaps. METHODS: Quality of life of 49 patients was assessed by means of the 14-item oral health impact profile (OHIP-14) and the medical outcomes study-short form-36 (SF-36) questionnaires 12 months after operation. RESULTS: Forty-one questionnaires were collected (84%). SF-36: the highest-scoring domain were physical role (92.9 ± 2.6) and bodily pain (82.6 ± 5.7), the lowest-scoring domain were vitality (61.5 ± 9.1), followed by role emotion (64.9 ± 6.8) and social functioning (65.2 ± 8.2). OHIP-14: the best-scoring domain were handicap (37.1 ± 15.1) and psychological disability (45.7 ± 11.9), the best-scoring domain were physical pain (64.2 ± 11.7) and functional limitation (61.9 ± 12.9). CONCLUSIONS: Radial forearm free flaps for reconstruction of oral defects after cancer resection could significantly influence the patients' quality of life.

[Inhibitory effects of antisense TGF beta1 on in vitro and in vivo proliferation of human bladder cancer cells].

OBJECTIVE: To investigate the inhibitory effects of antisense TGF beta1 on proliferation of human bladder transitional cell carcinoma in vitro and in vivo. METHODS: Human bladder carcinoma cell line EJ was transfected with pRevT beta-AS, a replication defective retroviral vector carried antisense TGF beta1 fragment. The growth of the transfected cells was observed in vitro and in vivo. TGF beta1 mRNA expression and protein expression were detected by RT-PCR and ELISA. The proliferative activity was evaluated by immunohistochemistry method. The ultrastructure of cells was observed by image analysis system and electron microscopy. Cell cycle was determined by flow cytometry. RESULTS: The expression of TGF beta1 mRNA and protein in EJ cells was inhibited by pRevT beta-AS, G(1) to S transition was restrained in cell cycle and cell proliferation decreased in vitro. The tumorigenesis and growth of EJ cells and DNA heteroploidy were reduced by antisense TGF beta1 in vivo. CONCLUSION: TGF beta1 plays a role in vitro proliferation and in vivo growth of bladder transitional cell carcinoma.