Silencing circSLAMF6 represses cell glycolysis, migration, and invasion by regulating the miR-204-5p/MYH9 axis in gastric cancer under hypoxia.

Gastric cancer (GC) is a malignant tumor of the digestive tract. Hypoxia plays an important role in the development of cancer, including GC. The present study aimed to investigate the role of circular RNA SLAMF6 (circSLAMF6) in the progression of GC under hypoxia. The expression of circSLAMF6, microRNA-204-5p (miR-204-5p) and myosin heavy chain 9 (MYH9) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). GC cells were maintained under hypoxia (1% O2) for experiments in vitro. Glucose consumption and lactate production were determined by a Glucose Assay Kit and a Lactate Assay Kit, respectively. Levels of all protein were detected by Western blot. Cell migration and invasion were examined by Transwell assay. The interaction between miR-204-5p and circSLAMF6 or MYH9 was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Murine xenograft model was established to explore the role of circSLAMF6 in vivo. CircSLAMF6 expression was increased in GC cells under hypoxia. Hypoxia promoted glycolysis, migration, and invasion in GC cells, which were reversed by circSLAMF6 knockdown. CircSLAMF6 was validated as a miR-204-5p sponge, and MYH9 was a target of miR-204-5p. Functionally, miR-204-5p inhibitor weakened the inhibition of circSLAMF6 knockdown on GC cell progression under hypoxia. Besides, MYH9 depletion suppressed glycolysis, migration, and invasion in GC cells under hypoxia. Importantly, circSLAMF6 deficiency inhibited tumor growth in vivo by regulating the miR-204-5p/MYH9 axis. CircSLAMF6 was involved in glycolysis, migration, and invasion by regulating the miR-204-5p/MYH9 axis in GC cells under hypoxia.

Fang X ，Bai Y ，Zhang L ，Ding S ... -  《-》

Circ_0027599 elevates RUNX1 expression via sponging miR-21-5p on gastric cancer progression.

Increasing evidence has shown that circular RNAs (circRNAs) serve as vital regulators in tumour progression. In this study, we focused on the functions of circ_0027599 in gastric cancer (GC) progression. The levels of circ_0027599, runt-related transcription factor 1 (RUNX1) mRNA and microRNA-21-5p (miR-21-5p) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The protein levels of RUNX1, E-Cadherin, vimentin and N-Cadherin were measured by Western blot assay. Cell viability, colony formation, metastasis and cell cycle process were evaluated by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, transwell assay and flow cytometry analysis, respectively. The interaction between circ_0027599 and miR-21-5p and the interaction between miR-21-5p and RUNX1 were verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The role of circ_0027599 in tumour growth in vivo was investigated by murine xenograft model assay. Circ_0027599 and RUNX1 were downregulated in GC tissues and cells. Circ_0027599 level was associated with the overall survival of GC patients. Circ_0027599 or RUNX1 overexpression inhibited GC cell viability, colony formation, migration, invasion and cell cycle process in vitro. For mechanism analysis, circ_0027599 positively regulated RUNX1 expression via functioning as the sponge for miR-21-5p. RUNX1 inhibition reversed circ_0027599 overexpression mediated malignant behaviours of GC cells. Moreover, circ_0027599 overexpression repressed tumour growth in vivo. Circ_0027599 overexpression repressed GC progression via modulation of miR-21-5p/RUNX1 axis, which might illumine a novel therapeutic target for GC.

Han J ，Yang Z ，Zhao S ，Zheng L ，Tian Y ，Lv Y ... -  《-》

Knockdown of Circ_0081143 Mitigates Hypoxia-Induced Migration, Invasion, and EMT in Gastric Cancer Cells Through the miR-497-5p/EGFR Axis.

Tang J ，Zhu H ，Lin J ，Wang H ... -  《-》

Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A.

Gastric cancer (GC) remains one of the most common malignancies worldwide. Increasing evidence has demonstrated that circRNAs serve as critical roles in human cancer, including GC. In the present study, we focused on the detailed function and mechanism of circ_0000144 on GC progression. The levels of circ_0000144, miR-623 and G-protein-coupled receptor, family C, group 5, member A (GPRC5A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Targeted relationships among circ_0000144, miR-623 and GPRC5A were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, colony formation, apoptosis, migration and invasion were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry and transwell assays. Measurement of glutamine and α-ketoglutarate (α-KG) levels was performed using a corresponding assay kit. GPRC5A protein expression was detected using Western blot. In vivo assays were used to explore the impact of circ_0000144 on tumor growth. Our data indicated that circ_0000144 was up-regulated and miR-623 was down-regulated in GC tissues and cells. Circ_0000144 interacted with miR-623 through directly binding to miR-623. Moreover, the knockdown of circ_0000144 weakened GC cell proliferation, colony formation, migration, invasion and glutaminolysis and accelerated cell apoptosis by up-regulating miR-623. GPRC5A was a direct target of miR-623 and circ_0000144 protected against GPRC5A repression through sponging miR-623. Furthermore, miR-623-mediated regulation on GC cell progression was reversed by the stored expression of GPRC5A. Additionally, circ_0000144 depletion inhibited tumor growth in vivo. Our study indicated that circ-0000144 knockdown repressed GC progression at least partly by regulating GPRC5A expression via sponging miR-623, illumining a novel therapeutic target for GC treatment.

Mi L ，Lei L ，Yin X ，Li N ，Shi J ，Han X ，Duan X ，Zhao M ，Han G ，Wang J ，Yin F ... -  《-》

LncRNA HULC promotes the progression of gastric cancer by regulating miR-9-5p/MYH9 axis.

Long non-coding RNAs (lncRNAs) highly upregulated in liver cancer (HULC) has been identified as an oncogene involved in many human cancers. Herein, we aimed to further explore the role and molecular mechanism of HULC in gastric cancer (GC) progression. The levels of HULC, miR-9-5p and myosin heavy chain 9 (MYH9) mRNA were detected by qRT-PCR. The targeted interaction between HULC and miR-9-5p was verified by dual-luciferase reporter and RNA pull-down assays. Cell proliferation assay, cell colony formation, flow cytometry and transwell assay were used to determine cell proliferation, colony formation, apoptosis and migration and invasion, respectively. Xenograft assay was used to observe the effect of HULC on GC growth in vivo. Our results revealed that HULC was upregulated and miR-9-5p was downregulated in GC, and both were associated with clinicopathologic features of GC patients. A positive correlation was found between HULC expression and epithelial-to-mesenchymal transition (EMT) of GC tissues. Moreover, HULC repressed miR-9-5p expression by binding to miR-9-5p. The regulatory effects of HULC knockdown on GC cell proliferation, migration, invasion, EMT and apoptosis were reversed by introduction of anti-miR-9-5p. HULC regulated MYH9 expression by acting as a molecular sponge of miR-9-5p in GC cells. HULC knockdown inhibited tumor growth in vivo. In conclusion, our data demonstrated that HULC knockdown repressed GC progression at least partly by regulating miR-9-5p/MYH9 axis.

Liu T ，Liu Y ，Wei C ，Yang Z ，Chang W ，Zhang X ... -  《-》