Analysis of SEMA3B methylation and expression patterns in gastric cancer tissue and cell lines

Chen, Renpin; Zhuge, Xiaoju; Huang, Zhiming; Lu, Deyi; Ye, Xiaohua; Chen, Chao; Yu, Jieyu; Lu, Guangrong

doi:10.3892/or.2014.2972

Cited by 21 publications

(14 citation statements)

References 29 publications

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“…Hypermethylation often reduces the mRNA levels not only of SEMA3B but also of some other genes of the LUCA region in tumors; e.g., RASSF1A , BLU , and CACNA2D2 [ 36 – 38 ]. SEMA3B methylation has been observed in various types of cancer, including lung, liver, gallbladder, gastric, breast and oral carcinomas, and neuroblastoma [ 17 , 54 – 61 ]. However, these studies included only the CpG-island, which, according to the NCBI database ( http://www.ncbi.nlm.nih.gov/ ), belongs to the first intron (+1350..+1700 bp from SEMA3B 5’-end) of SEMA3B .…”

Section: Discussionmentioning

confidence: 99%

Tumor Suppressor Function of the SEMA3B Gene in Human Lung and Renal Cancers

et al. 2015

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The SEMA3B gene is located in the 3p21.3 LUCA region, which is frequently affected in different types of cancer. The objective of our study was to expand our knowledge of the SEMA3B gene as a tumor suppressor and the mechanisms of its inactivation. In this study, several experimental approaches were used: tumor growth analyses and apoptosis assays in vitro and in SCID mice, expression and methylation assays and other. With the use of the small cell lung cancer cell line U2020 we confirmed the function of SEMA3B as a tumor suppressor, and showed that the suppression can be realized through the induction of apoptosis and, possibly, associated with the inhibition of angiogenesis. In addition, for the first time, high methylation frequencies have been observed in both intronic (32-39%) and promoter (44-52%) CpG-islands in 38 non-small cell lung carcinomas, including 16 squamous cell carcinomas (SCC) and 22 adenocarcinomas (ADC), and in 83 clear cell renal cell carcinomas (ccRCC). Correlations between the methylation frequencies of the promoter and the intronic CpG-islands of SEMA3B with tumor stage and grade have been revealed for SCC, ADC and ccRCC. The association between the decrease of the SEMA3B mRNA level and hypermethylation of the promoter and the intronic CpG-islands has been estimated in renal primary tumors (P < 0.01). Using qPCR, we observed on the average 10- and 14-fold decrease of the SEMA3B mRNA level in SCC and ADC, respectively, and a 4-fold decrease in ccRCC. The frequency of this effect was high in both lung (92-95%) and renal (84%) tumor samples. Moreover, we showed a clear difference (P < 0.05) of the SEMA3B relative mRNA levels in ADC with and without lymph node metastases. We conclude that aberrant expression and methylation of SEMA3B could be suggested as markers of lung and renal cancer progression.

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Section: Discussionmentioning

confidence: 99%

Tumor Suppressor Function of the SEMA3B Gene in Human Lung and Renal Cancers

et al. 2015

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“…143,144 Sema3B:The sema3B gene was identified along with sema3F as a tumor suppressor gene whose function is lost in small cell lung carcinoma cells by a variety of mechanisms that include promoter methylation and loss of heterozygosity. 91,[145][146][147][148][149][150] Sema3B also functions as an endogenous inhibitor of endometrial cancer, 151 and in oral squamous cell carcinoma in which its expression is inhibited as a result of promoter methylation. 152 In agreement with these observations single nucleotide polymorphisms in the sema3B gene were also found to be associated with poor prognosis of prostate cancer.…”

Section: Semaphorins As Regulators Of Tumor Progressionmentioning

confidence: 99%

The role of the semaphorins in cancer

Neufeld

Mumblat

Smolkin

et al. 2016

Cell Adhesion & Migration

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The semaphorins were initially characterized as axon guidance factors, but have subsequently been implicated also in the regulation of immune responses, angiogenesis, organ formation, and a variety of additional physiological and developmental functions. The semaphorin family contains more then 20 genes divided into 7 subfamilies, all of which contain the signature sema domain. The semaphorins transduce signals by binding to receptors belonging to the neuropilin or plexin families. Additional receptors which form complexes with these primary semaphorin receptors are also frequently involved in semaphorin signaling. Recent evidence suggests that semaphorins also fulfill important roles in the etiology of multiple forms of cancer. Some semaphorins have been found to function as bona-fide tumor suppressors and to inhibit tumor progression by various mechanisms while other semaphorins function as inducers and promoters of tumor progression. The semaphorin familyThe semaphorin family members are divided into 8 subclasses of which subclasses 1 and 2 contain invertebrate semaphorins while subclasses 3-7 contain the 22 vertebrate semaphorins. The 8th subclass contains viral semaphorins. In early publications, semaphorins were assigned confusing names. This situation was rectified by the adoption of a unified nomenclature in which sema is followed by the subclass number and by alphabetic designation within the subclass.1 Semaphorins are characterized by the presence of a »500 amino-acids long sema domain located close to their N-termini which is also present in semaphorin receptors of the plexin family, and by a plexin-semaphorin-integrin (PSI) domain located downstream to the sema domain. The sema domain is essential for semaphorin activity and plays a role in the determination of the receptor binding specificity.2 The sema domains of several different semaphorins were characterized by X-ray crystallography revealing a b propeller topology.3-5 Different semaphorin subclasses are characterized by class specific structural motifs. Thus, the vertebrate semaphorins belonging to classes 3, 4 and 7 contain immunoglobulin like domains, class-5 semaphorins contain thrombospondin repeats and class-3 semaphorins contain a basic domain. Class-3 semaphorins are the only vertebrate semaphorins produced as secreted proteins while other vertebrate semaphorins are membrane anchored or trans-membrane proteins that can be further processed into soluble forms by proteolytic cleavage (Fig.

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“…It is necessary to study the roles of other TSGs at this region in GCA tumorigenesis. Semaphorin 3B (SEMA3B), located on 3p21.3, is frequently inactivated in several types of carcinomas [11][12][13][14][15]. SEMA3, the only secreted soluble molecules of semaphorins family, was first identified as glycoproteins that negatively mediate neuronal guidance by binding to neuropilin and repelling neurons away from the source of SEMA3 [16].…”

Section: Introductionmentioning

confidence: 99%

“…The following studies have demonstrated that SEMA3B play inhibitory roles in tumor proliferation and angiogenesis [17]. Moreover, like other TSGs located at 3p21.3, the inactivation of SEMA3B in tumors may be caused by multiple mechanisms including allelic loss and aberrant CpG site methylation [11,14,15,[18][19][20]. However, the critical CpG sites and exact roles of SEMA3B in GCA have not been clarified.…”

Section: Introductionmentioning

confidence: 99%

MiR-6872 host gene SEMA3B and its antisense lncRNA SEMA3B-AS1 function synergistically to suppress gastric cardia adenocarcinoma progression

et al. 2019

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Background Semaphorin 3B (SEMA3B) is frequently inactivated in several carcinomas. However, as the host gene of miR-6872, the roles of SEMA3B, antisense lncRNA SEMA3B-AS1, and miR-6872 in gastric cardia adenocarcinoma (GCA) tumorigenesis have not been clarified. Methods The expression levels of SEMA3B, SEMA3B-AS1, and miR-6872 were respectively detected by qRT-PCR, western blot, or immunohistochemical staining assays. The methylation status was determined by BGS and BS-MSP methods. In vitro assays were preformed to explore the biological effects of SEMA3B, SEMA3B-AS1, and miR-6872-5p in gastric cancer cells. Chromatin immunoprecipitation assay was used to detect the binding of protein to DNA. The interaction of SEMA3B-AS1 with MLL4 was identified by RNA immunoprecipitation and RNA pull-down assays. Results Frequent downregulation of SEMA3B, SEMA3B-AS1, and miR-6872 was detected in GCA tissues and gastric cancer cells. Aberrant hypermethylation of the promoter region was more tumor specific and was negatively correlated with the expression level of SEMA3B, SEMA3B-AS1, and miR-6872-5p. Transcription factor Sp1 activated SEMA3B or SEMA3B-AS1 transcription and CpG sites hypermethylation within promoter region eliminated Sp1 binding ability. Overexpression of SEMA3B and SEMA3B-AS1 inhibited gastric cancer cell proliferation, migration, and invasion in vitro. SEMA3B-AS1 induced the expression of SEMA3B by interacting with MLL4. ZNF143 might be the target gene of miR-6872-5p and miR-6872-5p functioning synergistically with SEMA3B to suppress cell invasion. Furthermore, SEMA3B, SEMA3B-AS1, and miR-6872-5p expression levels were associated with GCA patients' survival. Conclusions SEMA3B, SEMA3B-AS1, and miR-6872 may act as tumor suppressors and may serve as potential targets for antitumor therapy.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Analysis of SEMA3B methylation and expression patterns in gastric cancer tissue and cell lines

Cited by 21 publications

References 29 publications

Tumor Suppressor Function of the SEMA3B Gene in Human Lung and Renal Cancers

Tumor Suppressor Function of the SEMA3B Gene in Human Lung and Renal Cancers

The role of the semaphorins in cancer

MiR-6872 host gene SEMA3B and its antisense lncRNA SEMA3B-AS1 function synergistically to suppress gastric cardia adenocarcinoma progression

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