Formin-like 2 promotes angiogenesis and metastasis of colorectal cancer by regulating the EGFL6/CKAP4/ERK axis.

Increasing evidence indicates that angiogenesis plays a pivotal role in tumor progression. Formin-like 2 (FMNL2) is well-known for promoting metastasis; however, the molecular mechanisms by which FMNL2 promotes angiogenesis in colorectal cancer (CRC) remain unclear. Here, we found that FMNL2 promotes angiogenesis and metastasis of CRC in vitro and in vivo. The GDB/FH3 domain of FMNL2 directly interacts with epidermal growth factor-like protein 6 (EGFL6). Formin-like 2 promotes EGFL6 paracrine signaling by exosomes to regulate angiogenesis in CRC. Cytoskeleton associated protein 4 (CKAP4) is a downstream target of EGFL6 and is involved in CRC angiogenesis. Epidermal growth factor-like protein 6 binds to the N-terminus of CKAP4 to promote the migration of HUVECs by activating the ERK/MMP pathway. These findings suggest that FMNL2 promotes the migration of HUVECs and enhances angiogenesis and tumorigenesis in CRC by regulating the EGFL6/CKAP4/ERK axis. Therefore, the EGFL6/CKAP4/ERK axis could be a candidate therapeutic target for CRC treatment.

Underestimation of the number of hidden objects.

The perceptual representation of our environment does not only involve what we actually can see, but also inferences about what is hidden from our sight. For example, in amodal completion, simple contours or surfaces are filled-in behind occluding objects allowing for a complete representation. This is important for many everyday tasks, such as visual search, foraging, and object handling. Although there is support for completion of simple patterns from behavioral and neurophysiological studies, it is unclear if these mechanisms extend to complex, irregular patterns. Here, we show that the number of hidden objects on partially occluded surfaces is underestimated. Observers did not consider accurately the number of visible objects and the proportion of occlusion to infer the number of hidden objects, although these quantities were perceived accurately and reliably. However, visible objects were not simply ignored: estimations of hidden objects increased when the visible objects formed a line across the occluder and decreased when the visible objects formed a line outside of the occluder. Confidence ratings for numerosity estimation were similar for fully visible and partially occluded surfaces. These results suggest that perceptual inferences about what is hidden in our environment can be very inaccurate und underestimate the complexity of the environment.

The lncRNA SOX2OT rs9839776 C>T Polymorphism Indicates Recurrent Miscarriage Susceptibility in a Southern Chinese Population.

Genetic susceptibility may be involved in the onset of recurrent miscarriage. Previous studies have shown that some genetic polymorphisms that regulate cell migration are associated with susceptibility to recurrent miscarriage. The SOX2 overlapping transcript (SOX2OT) may regulate the migration and invasion of multiple tumor cells and is related to susceptibility to various diseases. However, whether lncRNA SOX2OT polymorphisms are related to recurrent miscarriage susceptibility is unclear. Therefore, we investigated the relationship between the lncRNA SOX2OT rs9839776 C>T polymorphism and recurrent miscarriage susceptibility. We recruited 570 subjects with recurrent miscarriage and 578 healthy control subjects from a population in southern China and used the TaqMan method for genotyping. We found a significant association between the rs9839776 CT genotype in the SOX2OT gene and an increased risk for recurrent miscarriage (CT vs CC: adjusted OR = 1.357, 95%CI = 1.065 - 1.728, P = 0.0134). However, we did not observe any significant associations between the recurrent miscarriage risk and the number of miscarriages in different age groups. In conclusion, our study indicated that the rs9839776 CT genotype may contribute to an increased risk of recurrent miscarriage in the southern Chinese population and that rs9839776 may act as a prognostic biomarker in recurrent miscarriage patients. However, an experiment-based study with a larger sample size should be performed to confirm these results.

Significance of FBX8 in progression of gastric cancer.

F-box only protein 8 (FBX8), a novel component of F-box proteins, has recently been observed in several malignancies. However, its clinical implication in the progression of gastric cancer still remains unclear. The aim of this study was to explore the role of FBX8 in gastric cancer (GC) and analyze its correlation with tumor progression and prognosis. The expression of FBX8 in GC cell lines and matched pairs of fresh gastric cancer tissues were detected by real-time RT-PCR and Western blotting. Immunohistochemistry was used to analyze clinicopathological patterns of FBX8 in 136 cases of clinical paraffin-embedded GC tissues. A series of functional assays were conducted to evaluate the effect of FBX8 on proliferation and invasion in vitro and metastasis in vivo. FBX8 was markedly down-regulated in GC tissues compared to adjacent normal tissues. Patients with low FBX8 had shorter overall survival time and poor prognosis. Knocking down FBX8 obviously promoted proliferation and invasion in BGC823 cells, while over-expression of FBX8 in SGC7901 and AGS cells had the opposite effects. Moreover, FBX8 was sufficient to suppress metastasis in nude mice. Down-regulation of FBX8 significantly correlates with invasion, metastasis and poor survival time in GC patients. FBX8 may serve as a promising therapeutic target for inhibition of GC metastasis.

[Etiology analysis for hospitalized hypertensive patients: 10 years report from the department of hypertension (1999 - 2008)].

OBJECTIVE: To analyze etiology of hospitalized hypertensive patients in the department of hypertension from 1999 to 2008. METHODS: This retrospective study was performed to analyze the etiology of hospitalized hypertensive patients in department of hypertension and to show the distribution change of hypertension from 1999 to 2008. RESULTS: (1) There were 5867 (75.1%) patients with essential hypertension and 1942 (24.9%) patients with secondary hypertension (SH). (2) The prevalence rate of SH increased significantly during the 10 years (χ(2) = 387.621, P < 0.001) and was higher in 2008 than in 1999 (39.3% vs. 9.5%, P < 0.05). The prevalence of obstructive sleep apnea syndrome (OSAS) and primary aldosteronism (PA) in 2008 increased 38.3 and 1.8 times respectively than in 1999 (χ(2) = 304.025, P < 0.001; χ(2) = 42.845, P < 0.001) and other SH remained unchanged. (3) The prevalence of PA complicated with OSAS increased significantly in recent five years (χ(2) = 26.376, P < 0.001). Incidence of OSAS was 23.9% in PA patients and incidence of PA was 6.7% in OSAS patients. CONCLUSIONS: With the insights gained on hypertension mechanism and the development of new diagnostic technology, percent of diagnosed SH increased remarkably in recent years in hospitalized hypertensive patients in our department of hypertension. OSAS and PA are the leading causes of SH.

MicroRNA-206 functions as a tumor suppressor in colorectal cancer by targeting FMNL2.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the world. MicroRNAs play important roles in the progression of CRC. This study aimed to investigate the role of miR-206 and its novel mechanism in the invasion and metastasis of CRC. METHODOLOGY: Real-time RT-PCR or Western blotting was used to detect the expressions of miR-206, FMNL2 and c-MET in CRC cell lines and tissues. Luciferase reporter assays were conducted to detect the associations between miR-206 and 3'UTRs of FMNL2 and c-MET. A series of loss-of-function and gain-of-function assays were performed to evaluate the effect of miR-206 on the proliferation, invasion and metastasis of CRC cells. RESULTS: miR-206 was significantly down-regulated in CRC tissues and correlated closely with differentiation, lymphatic metastasis and serosal invasion. miR-206 suppressed CRC cell proliferation by arresting CRC cells in the G1/G0 phase and accelerating apoptosis. miR-206 also inhibited cell invasion and lung metastasis in CRC cells. Mechanically, FMNL2 and c-MET were identified as direct targets of miR-206. And FMNL2 rescued the suppression of miR-206 in the proliferation and invasion of CRC cells. CONCLUSIONS: This study revealed functional and mechanistic links between miR-206 and oncogene FMNL2 and c-MET in the progression of CRC. miR-206 functioned as a tumor suppressor in the progression of CRC by targeting FMNL2 and c-MET. Restoration of miR-206 expression may represent a promising therapeutic approach for targeting malignant CRC.

EML4-ALK translocation is associated with early onset of disease and other clinicopathological features in Chinese female never-smokers with non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation is resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib, but responds to the ALK-TKI crizotinib. Characterization of EML4-ALK translocation may provide invaluable information to facilitate disease diagnosis and improve the outcome of customized treatment. Although the occurrence of EML4-ALK translocation is likely to be affected by the smoking habits and gender of patients, the translocation has not been characterized extensively in female never-smokers with NSCLC. Therefore, 280 female never-smokers that were diagnosed with NSCLC were enrolled in the present study, and characteristics of EML4-ALK translocation, including the frequency, were determined in these NSCLC patients. EML4-ALK fusion variants were detected using Multiplex one-step reverse transcription-polymerase chain reaction and subsequently confirmed by DNA sequencing and Vysis ALK Break Apart fluorescence in situ hybridization analysis. The EML4-ALK fusion variants were detected in 21 carcinoma tissue specimens, accounting for 7.5% of the enrolled patients. Out of these patients with EML4-ALK fusion variants, EML4-ALK fusion variant 1 was identified in 12 patients, indicating that variant 1 is the most common type of EML4-ALK fusion gene in the present cohort of patients. ALK mRNA was aberrantly expressed in all the tissues with EML4-ALK translocation, but not in the carcinoma tissues without EML4-ALK translocation. In addition, the EML4-ALK translocation was more frequently found in younger patients. The median age of patients with EML4-ALK translocation was 50.95±2.29 years, which was significantly younger (P<0.01) than the median age of the patients without EML4-ALK translocation (57.15±0.56). The EML4-ALK translocation was detected exclusively in undifferentiated tumors that were graded as poorly- or moderately-differentiated carcinomas and suspected to be more malignant compared with well-differentiated tumors. In summary, the present study found that 7.5% of patients with NSCLC that are female never-smokers harbor EML4-ALK translocations, which are associated with the aberrant expression of ALK mRNA, early onset of disease and undifferentiated carcinomas.

Etiology analysis for hospitalized hypertensive patients: 10 years report from the department of hypertension (1999 - 2008) / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze etiology of hospitalized hypertensive patients in the department of hypertension from 1999 to 2008.</p><p><b>METHODS</b>This retrospective study was performed to analyze the etiology of hospitalized hypertensive patients in department of hypertension and to show the distribution change of hypertension from 1999 to 2008.</p><p><b>RESULTS</b>(1) There were 5867 (75.1%) patients with essential hypertension and 1942 (24.9%) patients with secondary hypertension (SH). (2) The prevalence rate of SH increased significantly during the 10 years (χ(2) = 387.621, P < 0.001) and was higher in 2008 than in 1999 (39.3% vs. 9.5%, P < 0.05). The prevalence of obstructive sleep apnea syndrome (OSAS) and primary aldosteronism (PA) in 2008 increased 38.3 and 1.8 times respectively than in 1999 (χ(2) = 304.025, P < 0.001; χ(2) = 42.845, P < 0.001) and other SH remained unchanged. (3) The prevalence of PA complicated with OSAS increased significantly in recent five years (χ(2) = 26.376, P < 0.001). Incidence of OSAS was 23.9% in PA patients and incidence of PA was 6.7% in OSAS patients.</p><p><b>CONCLUSIONS</b>With the insights gained on hypertension mechanism and the development of new diagnostic technology, percent of diagnosed SH increased remarkably in recent years in hospitalized hypertensive patients in our department of hypertension. OSAS and PA are the leading causes of SH.</p>