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

Abstract

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.

Identification and validation of stemness-related lncRNA prognostic signature for breast cancer

“…LINC00668 promoted tumorigenesis and progression and indicated poor prognosis in not only breast cancer but also other cancers, such as colorectal cancer, hepatocellular carcinoma and non-small-cell lung cancer [ 25 – 28 ]. SEMA3B-AS1 might serve as a new tumor suppressor to inhibit the development of hepatocellular carcinoma, esophageal squamous cell carcinoma and gastric cardia adenocarcinoma [ 29 – 31 ]. Consistent with our results, LINC00578 and LINC00668, as high-risk BCSC-related lncRNAs, were correlated with worse prognosis in breast cancer patients, whereas SEMA3B-AS1, as a low-risk BCSC-related lncRNA, was associated with better prognosis in breast cancer patients.…”

A pan-cancer study of class-3 semaphorins as therapeutic targets in cancer

“…For instance, SEMA3A induces invasion and correlates with poor survival in both pancreatic and colon cancers, but inhibits tumour invasion and metastasis in patients with prostate, breast, and lung cancer [9,13]. SEMA3B was found to play a pivotal tumour suppressor role in multiple cancers such as breast, gastric, and lung cancers [14][15][16][17]. SEMA3D is found to inhibit tumour growth in colorectal and breast cancers, but it correlates with metastatic disease and worse survival in patients with pancreatic cancer [15,18,19].…”

lncSAMM50 Enhances Adipogenic Differentiation of Buffalo Adipocytes With No Effect on Its Host Gene

“…The existing data suggest that lncRNA can play a role by regulating the expression of a host gene (Guo et al, 2019;Song et al, 2020), meaning that the function of a lncRNA is associated with its host gene. SAMM50 is the core component of the sorting and assembly machinery and plays a critical role in regulating mitochondrial dynamics and mitophagy (Liu et al, 2016;Jian et al, 2018), indicating a significant role of SAMM50 in energy metabolism.…”