scholarly journals Tumor-Suppressive MicroRNA-708 Targets Notch1 to Suppress Cell Proliferation and Invasion in Gastric Cancer

2018 ◽  
Vol 26 (9) ◽  
pp. 1317-1326 ◽  
Author(s):  
Xuyan Li ◽  
Xuanfang Zhong ◽  
Xiuhua Pan ◽  
Yan Ji
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Quantitative Polymerase Chain Reaction ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Inverse Association ◽  
Novel Target ◽  
Cancer Tissues ◽  
Proliferation And Invasion

Growing evidence has demonstrated that numerous microRNAs (miRNAs) may participate in the regulation of gastric carcinogenesis and progression. This phenomenon suggests that gastric cancer-related miRNAs can be identified as effective therapeutic targets for this disease. miRNA-708 (miR-708) has recently been reported to be aberrantly expressed in several types of cancer and contribute to carcinogenesis and progression. However, the expression level, biological roles, and underlying mechanisms of miR-708 in gastric cancer are poorly understood. Here we found that miR-708 was downregulated in gastric cancer tissues and cell lines. Downregulated miR-708 expression was significantly associated with lymphatic metastasis, invasive depth, and TNM stage. Further investigation indicated that ectopic expression of miR-708 prohibited cell proliferation and invasion in gastric cancer. Bioinformatics analysis showed that Notch1 was a potential target of miR-708. Notch1 was further confirmed as a direct target gene of miR-708 in gastric cancer by dual-luciferase reporter assay, reverse transcription quantitative polymerase chain reaction, and Western blot analysis. Furthermore, an inverse association was found between miR-708 and Notch1 mRNA levels in gastric cancer tissues. In addition, restored Notch1 expression rescued the inhibitory effects on gastric cancer cell proliferation and invasion induced by miR-708 overexpression. Our findings highlight the tumor-suppressive roles of miR-708 in gastric cancer and suggest that miR-708 may be investigated as a novel target for gastric cancer treatment.

scholarly journals miR-299-3p suppresses cell progression and induces apoptosis by downregulating PAX3 in gastric cancer

2021 ◽  
Vol 16 (1) ◽  
pp. 266-276
Author(s):  
Zhenfen Wang ◽  
Qing Liu ◽  
Ping Huang ◽  
Guohao Cai
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Western Blot ◽  
Luciferase Reporter ◽  
Reporter System ◽  
Western Blot Assay ◽  
Normal Tissues ◽  
Cell Progression ◽  
Luciferase Reporter System ◽  
Proliferation And Invasion

Abstract Gastric cancer (GC) is ranked the fourth leading cause of cancer-related death, with an over 75% mortality rate worldwide. In recent years, miR-299-3p has been identified as a biomarker in multiple cancers, such as acute promyelocytic leukemia, thyroid cancer, and lung cancer. However, the regulatory mechanism of miR-299-3p in GC cell progression is still largely unclear. Cell viability and apoptosis tests were performed by CCK8 and flow cytometry assay, respectively. Transwell assay was recruited to examine cell invasion ability. The interaction between miR-299-3p and PAX3 was determined by the luciferase reporter system. PAX3 protein level was evaluated by western blot assay. The expression of miR-299-3p was downregulated in GC tissues and cell lines (MKN-45, AGS, and MGC-803) compared with the normal tissues and cells. Besides, overexpression of miR-299-3p significantly suppressed proliferation and invasion and promoted apoptosis in GC. Next, we clarified that PAX3 expression was regulated by miR-299-3p using a luciferase reporter system, qRT-PCR, and western blot assay. Additionally, downregulation of PAX3 repressed GC cell progression. The rescue experiments indicated that restoration of PAX3 inversed miR-299-3p-mediated inhibition on cell proliferation and invasion. miR-299-3p suppresses cell proliferation and invasion as well as induces apoptosis by regulating PAX3 expression in GC, representing desirable biomarkers for GC diagnosis and therapy.

scholarly journals MicroRNA-154 Inhibits the Growth and Invasion of Gastric Cancer Cells by Targeting DIXDC1/WNT Signaling

2018 ◽  
Vol 26 (6) ◽  
pp. 847-856 ◽  
Author(s):  
Jifu Song ◽  
Zhibin Guan ◽  
Maojiang Li ◽  
Sha Sha ◽  
Chao Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Inverse Correlation ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Gastric Cancer Cells ◽  
Cancer Cell Growth ◽  
Cancer Tissues

MicroRNAs (miRNAs) have emerged as pivotal regulators of the development and progression of gastric cancer. Studies have shown that miR-154 is a novel cancer-associated miRNA involved in various cancers. However, the role of miR-154 in gastric cancer remains unknown. Here we aimed to investigate the biological function and the potential molecular mechanism of miR-154 in gastric cancer. We found that miR-154 was significantly downregulated in gastric cancer tissues and cell lines. The overexpression of miR-154 significantly repressed the growth and invasion of gastric cancer cells. Bioinformatics analysis and Dual-Luciferase Reporter Assay data showed that miR-154 directly targeted the 3′-untranslated region of Dishevelled‐Axin domain containing 1 (DIXDC1). Real-time quantitative polymerase chain reaction and Western blot analyses showed that miR-154 overexpression inhibited DIXDC1 expression. An inverse correlation of miR-154 and DIXDC1 was also demonstrated in gastric cancer specimens. Overexpression of miR-154 also significantly suppressed the activation of WNT signaling. Moreover, restoration of DIXDC1 expression significantly reversed the inhibitory effect of miR-154 overexpression on the cell proliferation, invasion, and WNT signaling in gastric cancer cells. Overall, these results suggest that miR-154 inhibits gastric cancer cell growth and invasion by targeting DIXDC1 and could serve as a potential therapeutic target for the treatment of gastric cancer.

scholarly journals PITPNA-AS1 Activated by H3K27ac Sponged miR-98-5p to Regulate Cisplatin Resistance in Gastric Cancer

2021 ◽  
Author(s):  
Yaping Liu ◽  
Xu Zhao ◽  
Yinnan Chen ◽  
Gang Guo ◽  
Jiansheng Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Platinum Resistance ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
Proliferation And Apoptosis ◽  
Gastric Cancer Cell Lines ◽  
Cancer Tissues

Abstract To evaluate the expression of PITPNA-AS1 and miR-98-5p in gastric cancer tissues as well as their association with progression of gastric cancer, and investigate the role of PITPNA-AS1 and miR-98-5p in developing platinum resistance. RNA sequencing was used to identify candidate lncRNAs and microRNAs related to local recurrence of gastric cancer. qRT-PCR was used to investigate the expression of PITPNA-AS1 and miR-98-5p. CCK-8 and caspase3/7 activity were used to evaluate the cell proliferation and apoptosis rate. Dual luciferase reporter gene assay and RNA pull down were used to evaluate the cross talk between PITPNA-AS1 and miR-98-5p. PITPNA-AS1 and miR-98-5p could regulate cell proliferation and inhibit apoptosis in gastric cancer cell lines. Cisplatin and lobaplatin could significantly suppress the expression of PITPNA-AS1, which interacted with negatively regulated miR-98-5p expression. PITPNA-AS1 overexpression impaired the effect of platinum, which was partially reversed by downregulation of miR-98-5p knock down. In gastric cancer, PITPNA-AS1 and miR-98-5p could regulat cell growth, apoptosis and platinum resistance. They have the potential to be biomarkers and curative therapeutic targets. However, further research on molecular mechanisms are needed.

scholarly journals LncRNA SNHG15 modulates gastric cancer tumorigenesis by impairing miR-506-5p expression

2021 ◽  
Author(s):  
Zhiping Chen ◽  
Tianyu Zhong ◽  
Tao Li ◽  
Jinghua Zhong ◽  
Yang Tang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Tumor Development ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Ags Cells ◽  
Direct Target ◽  
Non Coding Rnas ◽  
Novel Target

The gastric cancer (GC) patients commonly have a poor prognosis due to its invasiveness and distant metastasis. Growing evidence proved that aberrant long non-coding RNAs (lncRNAs) expression contributes to tumor development and progression. LncRNA SNHG15 has been reported to be involved in many different kinds of cancer, while its role in GC remains unclear. In the present study, we found that SNHG15 was up-regulated in GC tissues and cell lines. Silencing SNHG15 suppressed proliferation migration, invasion and promoted apoptosis of AGS cells. More importantly, microRNA-506-5p (miR-506-5p) was predicted as a direct target of SNHG15 by binding its 3’-UTR and further verified using luciferase reporter assay. Meanwhile, the results of rescue experiments revealed that knockdown of miR-506-5p expression reversed the functional effects of SNHG15 silenced on cell proliferation, migration, invasion and apoptosis. In conclusion, our findings revealed that SNHG15 executed oncogenic properties in GC progression through targeting miR-506-5p, which might provide a novel target for the GC treatment.

scholarly journals MicroRNA-302b-3p Suppresses Cell Proliferation Through AKT Pathway by Targeting IGF-1R in Human Gastric Cancer

2017 ◽  
Vol 42 (4) ◽  
pp. 1701-1711 ◽  
Author(s):  
Bo Guo ◽  
Zhenghao Zhao ◽  
Zhen Wang ◽  
Qian Li ◽  
Xiaofei Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Biological Effects ◽  
Embryonic Stem ◽  
Luciferase Reporter ◽  
Human Gastric Cancer ◽  
Cancer Tissues

Background/Aims: MiR-302b is a major microRNA found in human embryonic stem cells and induced pluripotent stem cells. However, its function in gastric cancer progression remains unclear. Methods: Quantitative reverse transcription-PCR was performed to detect the expression levels of miR-302b-3p in gastric cancer tissues. MTT, colony formation, and flow cytometer analyses were conducted to explore the function of miR-302b-3p in MKN-45/SGC-7901 cells. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-302b-3p. Western blotting and RNA interference were used to evaluate the expression of the AKT signaling pathway and determine the mechanisms underlying miR-302b-3p-induced anti-tumor effects. Results: MiR-302b-3p expression was decreased in gastric cancer tissues and cell lines. Enforced expression of miR-302b suppressed cell proliferation and cell cycle G1-S transition and induced apoptosis. IGF-1R was found to be a direct target of miR-302b-3p, and silencing of IGF-1R resulted in the same biological effects as those induced by miR-302b-3p overexpression in gastric cancer cells. Importantly, both overexpression of miR-302b-3p and silencing of IGF-1R decreased AKT phosphorylation, which modulated AKT related cell cycle regulators (cyclin A2, cyclin D1, CDK2, and CDk6) and apoptotic protein Bax/Bcl-2. Conclusion: These results indicate the tumor suppressor role of miR-302b-3p in the pathogenesis of gastric cancer.

scholarly journals LncRNA SNHG20 promotes cell proliferation and invasion by suppressing miR-217 in ovarian cancer

2021 ◽  
Author(s):  
Xuefeng Xing ◽  
Ming An ◽  
Tonghua Chen
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Luciferase Reporter ◽  
Cancer Cell Proliferation ◽  
Transfected Cells ◽  
Cancer Tissues ◽  
Proliferation And Invasion

Abstract Background Ovarian cancer is the most common female gynecological malignancy. SNHG20, as a long non-coding RNA, has been proven to be an important regulator in the occurrence and development of various tumors. However, the potential mechanism of SNHG20 in ovarian cancer is unclear. Objective The present study was aimed to investigate the functions and mechanisms of SNHG20 in ovarian cancer. Methods The expression of SNHG20 and miR-217 in ovarian cancer tissues and cell lines was detected by qRT-PCR. CCK-8 assay was used to measure cell proliferation in transfected cells. The transwell assay was used to detect the relative invasion rate of transfected cells. The putative binding sites between SNHG20 and miR-217 were predicted by software LncBase v.2, and the interaction between SNHG20 and miR-217 was confirmed by dual-luciferase reporter assays and RIP assay. The rescue experiments were used to illustrate potential mechanisms. Results SNHG20 was upregulated in ovarian cancer tissues and cell lines. Overexpression of SNHG20 promoted ovarian cancer cell proliferation and invasion. MiR-217 was downregulated in ovarian cancer tissues and cells, and was negatively regulated by SNHG20. Moreover, miR-217 overexpression inhibited ovarian cancer cell proliferation and invasion. Furthermore, miR-217 mimic reversed the inhibitory effect of SNHG20 overexpression on the biological behavior of ovarian cancer cells. Conclusions SNHG20 promoted cell proliferation and invasion by sponging miR-217 in ovarian cancer. These results suggested that SNHG20 and miR-217 might provide new targets for therapeutic application in ovarian cancer.

scholarly journals MiR-1271 Inhibits Cell Proliferation, Invasion and EMT in Gastric Cancer by Targeting FOXQ1

2015 ◽  
Vol 36 (4) ◽  
pp. 1382-1394 ◽  
Author(s):  
Xiao-Jun Xiang ◽  
Jun Deng ◽  
Ya-Wen Liu ◽  
Lu-Ying Wan ◽  
Miao Feng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Tumor Stage ◽  
Luciferase Reporter ◽  
Regulation Mechanism ◽  
Mesenchymal Transition ◽  
Direct Target ◽  
Enhance Tumor Growth

Background/Aims: FOXQ1 overexpression has been reported to enhance tumor growth and invasion. However, the biological function of FOXQ1 and the mechanism underlying its upregulation in gastric cancer (GC) remain unknown. Methods: QPCR was used to detect the expression of miR-1271 and FOXQ1 in specimens from GC patients. FOXQ1-siRNA, and miR-1271 mimics and inhibitor were transfected into human MGC-803 and SGC-7901 cells. The transwell assay was used to examine the cell invasive ability. The regulation mechanism was confirmed by luciferase reporter assay. Markers of epithelial-mesenchymal transition (EMT) were detected by western blot analysis. Results: MiR-1271 was downregulated in both GC tissues and GC cell lines. The expression of miR-1271 was inversely correlated with tumor size (P = 0.017), tumor stage (P = 0.035), lymph node metastasis (P = 0.018), and TNM stage (P = 0.025). Ectopic expression of miR-1271 dramatically suppressed GC cell proliferation, invasion, and EMT. Furthermore, FOXQ1 was identified as a direct target of miR-1271. Knockdown of FOXQ1 inhibited GC cell malignant behavior, whereas FOXQ1 overexpression partially restored the suppression effects of miR-1271. Additionally, miR-1271 expression was negatively correlated with FOXQ1 in GC tissues. Conclusions: MiR-1271 inhibits cell proliferation, invasion, and EMT in GC by directly suppressing FOXQ1 expression.

scholarly journals Knockdown of LINC00665 inhibits proliferation and invasion of breast cancer via competitive binding of miR-3619-5p and inhibition of catenin beta 1

2020 ◽  
Vol 25 (1) ◽  
Author(s):  
Minhao Lv ◽  
Qixin Mao ◽  
Juntao Li ◽  
Jianghua Qiao ◽  
Xiuchun Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Quantitative Polymerase Chain Reaction ◽  
Polymerase Chain Reaction Analysis ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Protein Coding ◽  
Expression Levels ◽  
Reporter Assays ◽  
Proliferation And Invasion

Abstract Background Long intergenic non-protein coding RNA00665 (LINC00665) plays a crucial tumorigenic role in many cancers, such as gastric cancer and lung adenocarcinoma. However, its role and mechanism of action in the progression of breast cancer (BC) are unknown. Methods LINC00665 expression levels were determined using quantitative polymerase chain reaction analysis with BC tissues and cell lines. BC cell proliferation was tested by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, whereas BC cell migration and invasion capabilities were analyzed by performing transwell migration assays. Percentages of apoptotic cells were measured by flow cytometry. Interactions between LINC00665 and miR-3169-5p were examined by performing luciferase reporter assays, and the expression levels of proteins, such as β-catenin, were examined by western blot analysis. Results LINC00665 was expressed at high levels in BC tissues and cells. Upregulated LINC00665 expression correlated with tumor size and tumor, node, and metastasis stages, but not with the age of patients. LINC00665 knockdown inhibited BC cell proliferation, migration, and invasion, whereas it promoted apoptosis. Moreover, bioinformatics analysis and the luciferase reporter assay revealed that LINC00665 bound the microRNA (miR) miR-3619-5p. miR-3619-5p expression correlated negatively with LINC00665 expression in BC tissues. miR-3619-5p overexpression inhibited BC cell proliferation, migration, and invasion, but promoted apoptosis. Simultaneous knockdown of LINC00665 and miR-3619-5p led to increased cell proliferation, migration, and invasion, and inhibited apoptosis. Additionally, catenin beta 1, which encodes the β-catenin protein, was the target gene of miR-3619-5p. β-catenin expression clearly decreased after LINC00665 knockdown and miR-3619-5p overexpression, but increased after simultaneous knockdown of LINC00665 and miR-3619-5p. Conclusion LINC00665 knockdown inhibited BC cell proliferation and invasion by binding miR-3619-5p and inhibiting β-catenin expression.

Exosome-mediated transfer of miR-1290 promotes cell proliferation and invasion in gastric cancer via NKD1

2019 ◽  
Vol 51 (9) ◽  
pp. 900-907 ◽  
Author(s):  
Jiying Huang ◽  
Manru Shen ◽  
Meizhu Yan ◽  
Ying Cui ◽  
Zhenjun Gao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Negative Control ◽  
Luciferase Reporter ◽  
Serum Samples ◽  
Transmission Electron ◽  
Direct Target ◽  
Polymerase Chain ◽  
Proliferation And Invasion ◽  
Dual Luciferase Reporter Assay

Abstract Currently, exosomes rich in RNAs and proteins are regarded as vital mediators of intercellular communication. Here, we aimed to explore the effects of exosomal miR-1290 in gastric cancer (GC) and understand its mechanism of action on GC progression. We first isolated exosomes from serum samples of GC patients and healthy people and characterized them by transmission electron microscopy. Then, we examined the expression level of miR-1290 contained in the exosomes by quantitative reverse-transcription polymerase chain reaction and found that exosomal miR-1290 was overexpressed in GC patients and cell lines. Promotion of proliferation, migration, and invasiveness of GC cells was noted after they were incubated with the isolated miR-1290-rich exosomes compared with incubation with a negative control. Furthermore, we predicted that naked cuticle homolog 1 (NKD1) mRNA is a direct target of miR-1290 and confirmed their interaction by a dual luciferase reporter assay. NKD1 overexpression attenuated the stimulatory effects of miR-1290 on GC cells. Collectively, our results suggest that exosomal miR-1290 enhances GC cell proliferation and invasion by targeting NKD1 mRNA and downregulating NKD1 expression. A better understanding of this process may facilitate the development of novel therapeutic agents for GC.

scholarly journals HOTAIR Promotes Cisplatin Resistance of Nasopharyngeal Carcinoma Cells by Regulating Cell Proliferation, Invasion, and Apoptosis via miR-106a-5p/SOX4 Axis

2020 ◽  
Author(s):  
Wei Cao ◽  
Yi Sun ◽  
Long Liu ◽  
Junwei Yu ◽  
Jiabiao Ji ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Drug Resistance ◽  
Nasopharyngeal Carcinoma ◽  
Quantitative Polymerase Chain Reaction ◽  
Malignant Neoplasm ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Multi Drug Resistance ◽  
Migration And Invasion ◽  
Proliferation And Invasion

Abstract Background: Nasopharyngeal carcinoma (NPC) is a highly malignant neoplasm originating from nasopharyngeal mucosa, and the emergence of multi-drug resistance poses a huge challenge for clinical treatment of NPC. LncRNA HOTAIR (HOX antisense intergenic RNA) has been reported to be associated with many malignancies, including NPC. However, the underlying mechanisms of HOTAIR involved in drug resistance in NPC are obscure.Methods: Quantitative polymerase chain reaction (qPCR) was employed to determine the HOTAIR, miR-106a-5p and SOX4 expression in NPC tissues and cells. The target relationship between HOTAIR and miR-106a-5p or miR-106a-5p and SOX4 was determined using dual-luciferase reporter assay. Cell proliferation, apoptosis, migration and invasion were explored using Cell counting kit-8 (CCK-8), flow cytometer and Transwell assays. The protein levels were confirmed using western blot.Results: Our study showed that HOTAIR was upregulated in cisplatin (DDP)-resistant NPC tissues and cells. HOTAIR knockdown decreased the DDP resistance, drug resistance related gene expression, cell proliferation and invasion, and promoted apoptosis of C666-1/DDP and CNE2/DDP cells. Mechanism researches displayed that miR-106a-5p was down-regulated in DDP-resistant NPC tissues and cells. miR-106a-5p directly bound with HOTAIR and was regulated by HOTAIR. SOX4 was inhibited by miR-106a-5p at a posttranscriptional level, and the transfection of miR-106a-5p reversed the upregulation of SOX4 caused by HOTAIR overexpression. Increase or decrease of miR-106a-5p suppressed the effect of HOTAIR upregulation or downregulation on DDP resistance, cell proliferation, invasion and apoptosis of C666-1/DDP and CNE2/DDP cells. Moreover, the transfection of SOX4 siRNA reversed the decrease of DDP resistance, cell proliferation and invasion, and rescued the increase of apoptosis induced by miR-106a-5p inhibition. Conclusions: These data suggested that HOTAIR enhanced DDP resistance of C666-1/DDP and CNE2/DDP cells by affecting cell proliferation, invasion, and apoptosis via miR-106a-5p/SOX4 axis.

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