Knockdown of long non-coding RNA HOXD-AS1 inhibits gastric cancer cell growth via inactivating the JAK2/STAT3 pathway

Li, Zheng; Chen, Jiangtao; Zhou, Zhiyong; He, Zhikuan

doi:10.1177/1010428317705335

Cited by 45 publications

(28 citation statements)

References 27 publications

(35 reference statements)

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“…As has been confirmed by extensive studies, activated AKT and STAT3 signaling is closely associated with the biological functions of many tumors, also associated with GC (17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Western blot analyses demonstrated that the activity of AKT and STAT3 signaling was decreased following inhibition of STMN expression (P<0.05; Fig.…”

Section: Stmn Promotes the Development Of Gc Via Different Pathwayssupporting

confidence: 61%

Stathmin gene silencing suppresses proliferation, migration and invasion of gastric cancer cells via AKT/sCLU and STAT3 signaling

et al. 2019

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Globally, gastric cancer is the fifth most common malignancy, with high rates of incidence and mortality. The high mortality rate and poor prognosis of gastric cancer are closely associated with its profound invasiveness, high incidence of metastasis, rapid proliferation, and high rate of recurrence. Previous studies have confirmed that stathmin (STMN) has an important role in the occurrence, development and prognosis of gastric cancer. However, the detailed mechanisms by which STMN affects these processes remain unclear. The aim of the present study was to determine how STMN promotes invasion, migration and proliferation in gastric cancer tumor cells. The results of immunohistochemistry indicated that STMN is overexpressed in stomach neoplasm tissues, and that it is associated with migration, invasion, proliferation and anti-apoptotic states of gastric cancer cells. The secretory proteins of gastric cancer cells with or without STMN knockdown were further analyzed using the isobaric tags for relative and absolute quantitation method to identify differentially expressed proteins verified by reverse transcription-quantitative polymerase chain reaction and western blot analysis. Inhibition of STMN decreases the levels of clusterin, cystatin C and matrix metalloproteinases, followed by inhibiting the protein kinase B and signal transducer and activation of transcription activation. These findings suggest that STMN could be a promising therapeutic target for gastric cancer.

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Section: Stmn Promotes the Development Of Gc Via Different Pathwayssupporting

confidence: 61%

Stathmin gene silencing suppresses proliferation, migration and invasion of gastric cancer cells via AKT/sCLU and STAT3 signaling

et al. 2019

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“…For GO analysis, we found the DEGs could be significantly enriched in the GO terms that corresponding to biological phenotypes caused by HOXD-AS1 silencing, such as regulation of cell proliferation, regulation of cell migration, cell cycle arrest, and apoptotic process. 29 Taken together, this paper revealed that HOXD-AS1, an overexpressed lncRNA in HCC tissues/cell lines, was correlated with histologic grade and contributed to HCC progression through affecting the proliferation, migration, invasion and cell cycle progression of HCC cells via MEK/ ERK signaling pathway, suggesting that HOXD-AS1 might be a feasible biomarker and therapeutic target for HCC. For KEGG analysis, the enrichment results demonstrated HOXD-AS1 was likely to affect P53, TNF, and MAPK signaling pathway, and we further validated that HOXD-AS1 silencing could inhibit the MAPK signaling pathway in Bel-7402 cells through detecting the activity of MEK1/2 and ERK1/2 pathway using Western blot analysis.…”

Section: Discussionmentioning

confidence: 66%

Silencing of long noncoding RNA HOXD‐AS1 inhibits proliferation, cell cycle progression, migration and invasion of hepatocellular carcinoma cells through MEK/ERK pathway

Sun

Guo

Bie

et al. 2019

J of Cellular Biochemistry

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Accumulating findings reveal that long noncoding RNAs (lncRNAs) as crucial regulatory molecules serve vital functions in the progression of hepatocellular carcinoma (HCC). This study aims to investigate the biological roles and mechanisms of lncRNA HOXD cluster antisense RNA 1 (HOXD‐AS1) in HCC cells based on transcriptome analysis. The Cancer Genome Atlas data analysis and experimental validation showed that HOXD‐AS1 was increased in HCC tissues/cell lines and positively relevant to histologic grade. The subcellular localization results indicated HOXD‐AS1 was dispersed both in the nucleus as well as the cytoplasm of HCC cells. In vitro loss‐of‐function experiments revealed that silencing of HOXD‐AS1 could dramatically suppress the proliferation, migration, and invasion, and induce S or/and G2/M phase cell cycle arrest as well as apoptosis of Bel‐7402 and MHCC97H cells accompanying the changes in expression levels of cyclin B1, cyclin D1, BCL‐2, BAX, and MMP2. In vivo assay also showed that HOXD‐AS1 silencing could markedly reduce xenograft tumor volume and weight of HCC cells. Transcriptome and bioinformatic analysis indicated that a total of 1103 genes were significantly altered by HOXD‐AS1 silencing, of which 132 genes exhibited a significant correlation with HOXD‐AS1 expression in HCC tissues. Gene Ontology (GO) enrichment analysis revealed differentially expressed genes were remarkably enriched in several cancer‐related biological processes (cell proliferation, cell cycle, apoptosis, migration, angiogenesis, and hypoxic response). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that HOXD‐AS1 has the potential to affect p53, tumor necrosis factor (TNF), mitogen‐activated protein kinase (MAPK) pathway, and Western blot results further validated that HOXD‐AS1 silencing could inhibit the MEK/ERK pathway in Bel‐7402 cells. Collectively, HOXD‐AS1, as an oncogenic lncRNA, might exert crucial functions in HCC progression and serve as a potential diagnostic biomarker and therapeutic target for HCC.

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“…HOXD antisense growth-associated long noncoding RNA (HAGLR, also known as HOXD-AS1) is understood to be capable of influencing tumor metastasis, recurrence, and clinical prognosis (20)(21)(22). HAGLR has been speculated to function as a biomarker as well as a potential therapeutic target for predicting gastric cancer and determining its progression (23). Hence, we subsequently asserted the hypothesis that the down-regulating HAGLR may suppress EC progression, with the central objective to identify the role of the HAGLR/miR-143-5p/LAMP3 axis in the progression of EC.…”

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confidence: 99%

Long noncoding RNA HAGLR acts as a microRNA‐143‐5p sponge to regulate epithelial‐mesenchymal transition and metastatic potential in esophageal cancer by regulating LAMP3

et al. 2019

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Homeobox D gene cluster antisense growth‐associated long noncoding RNA (HAGLR) functions as a crucial regulator in the progression and development of human cancers. We analyzed effects of HAGLR, microRNA (miR)‐143‐5p and lysosome‐associated membrane glycoprotein (LAMP)3 on esophageal cancer (EC) and the related mechanisms. Microarray analysis was used to screen out EC‐related genes and the regulation network among HAGLR, miR‐143‐5p, and LAMP3. The regulatory mechanisms of HAGLR and miR‐143‐5p in EC were analyzed following the treatment of miR‐143‐5p mimic, miR‐143‐5p inhibitor, HAGLR vector, or small interfering RNA against HAGLR in EC cells. The expression of N‐cadherin, vimentin, Twist1, Snail1, and E‐cadherin as well as the abilities of cell proliferation, invasion, and migration were measured. The effects of the HAGLR/miR‐143‐5p/LAMP3 axis were determined in vivo by assessing tumor formation in nude mice. The expression of HAGLR and LAMP3 was increased, whereas that of miR‐143‐5p was diminished in EC tissues and cells. HAGLR could competitively bind to miR‐143‐5p, and miR‐143‐5p targeted LAMP3. Down‐regulated HAGLR or up‐regulated miR‐143‐5p increased E‐cadherin expression and significantly diminished expression of LAMP3, N‐cadherin, vimentin, Twist1, and Snail1. Moreover, down‐regulated HAGLR inhibited cell proliferation, invasion, migration, epithelial‐mesenchymal transition (EMT), and tumor growth. Moreover, down‐regulation of HAGLR inhibited LAMP3 expression by sponging miR‐143‐5p, thereby suppressing the progression of EC. Taken together, our results suggest HAGLR acts as a competing endogenous RNA of miR‐143‐5p to increase the expression of LAMP3, thus promoting EMT, proliferation, invasion, and migration in EC cells.—Yang, C., Shen, S., Zheng, X., Ye, K., Sun, Y., Lu, Y., Ge, H. Long noncoding RNA HAGLR acts as a microRNA‐143‐5p sponge to regulate epithelial‐mesenchymal transition and metastatic potential in esophageal cancer by regulating LAMP3. FASEB J. 33, 10490–10504 (2019). http://www.fasebj.org

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Knockdown of long non-coding RNA HOXD-AS1 inhibits gastric cancer cell growth via inactivating the JAK2/STAT3 pathway

Cited by 45 publications

References 27 publications

Stathmin gene silencing suppresses proliferation, migration and invasion of gastric cancer cells via AKT/sCLU and STAT3 signaling

Stathmin gene silencing suppresses proliferation, migration and invasion of gastric cancer cells via AKT/sCLU and STAT3 signaling

Silencing of long noncoding RNA HOXD‐AS1 inhibits proliferation, cell cycle progression, migration and invasion of hepatocellular carcinoma cells through MEK/ERK pathway

Long noncoding RNA HAGLR acts as a microRNA‐143‐5p sponge to regulate epithelial‐mesenchymal transition and metastatic potential in esophageal cancer by regulating LAMP3

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