CircFAM114A2 Inhibits Bladder Cancer Proliferation and Promotes Cisplatin Sensitivity via the miR-222-3p/P27 and miR-146a-5p/P21 Cascades

Abstract Background: Circular RNAs (circRNAs) are noncoding RNAs that have the structure of a covalently closed loop. Increasing data has proved that circRNA can influence the development and progression of tumors. CircFAM114A2 is generated from several exons of FAM114A2. However, the function and mechanisms of circFAM114A2 in bladder cancer (BCa) remain unclear. Methods: Here, to elucidate the potential roles of circFAM114A2 in BCa, we conducted RNA-sequencing on 5 pairs of BCa samples and screened for circRNAs. CircRNAs, microRNAs (miRNAs) and mRNAs, as well as levels of P27 and P21, in human cells and tissues were detected by qRT-PCR and western blot, respectively. CircRNA-miRNA interactions and miRNA-downstream mRNAs interactions were investigated by RNA pull-down assay and fluorescence in situ hybridization (FISH) or luciferase reporter assays, respectively. Then, the function of circFAM114A2 in BCa was explored using cell proliferation, cell cycle and tumorigenesis assays in nude mice. Finally, the function of circFAM114A2 in cisplatin chemo-sensitivity in BCa was detected by IC50 and tumor formation of xenograft in cisplatin-treated nude mice. Results: We discovered that circFAM114A2 levels were decreased in BCa cell lines and tissues. According to follow-up data, BCa patients with higher circFAM114A2 expression had better survival. Importantly, the levels of circFAM114A2 were associated with the histological grade of BCa. Overexpression of circFAM114A2 inhibited cell proliferation and increased sensitivity to cisplatin chemotherapy. Mechanistically, circFAM114A2 directly sponged miR-222-3p/miR-146a-5p and subsequently influenced the expression of the downstream target genes P27/P21, which, in turn, inhibited progression of BCa. Conclusion: In conclusion, circFAM114A2 acted as a tumor suppressor through a novel circFAM114A2/miR-222-3p/P27 and circFAM114A2/miR-146a-5p/P21 pathway. CircFAM1142 has therefore great potential as a prognostic biomarker and therapeutic target for BCa.

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CircFAM114A2 Inhibits Bladder Cancer Proliferation and Promotes Cisplatin Sensitivity via the miR-222-3p/P27 and miR-146a-5p/P21 Cascades

10.21203/rs.3.rs-108114/v1 ◽

2020 ◽

Author(s):

Jiancheng Lv ◽

Zijian Zhou ◽

Jingzi Wang ◽

Xiao Yang ◽

Hao Yu ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Progression ◽

Nude Mice ◽

Target Genes ◽

Histological Grade ◽

Tumor Formation ◽

Luciferase Reporter ◽

Circular Rnas

Abstract Background: Circular RNAs (circRNAs) are noncoding RNAs that have the structure of a covalently closed loop. Increasing data has proved that circRNA can influence the development and progression of tumors. CircFAM114A2 is generated from several exons of FAM114A2. However, the function and mechanisms of circFAM114A2 in bladder cancer (BCa) remain unclear. This research aimed to reveal that circFAM114A2 inhibits bladder cancer progression and improves sensitivity of cisplatin chemotherapy by inducing G1/S cell cycle arrest via novel miR-222-3p/P27 and miR-146a-5p/P21 cascades.Methods: Here, to elucidate the potential roles of circFAM114A2 in BCa, we conducted RNA-sequencing on 5 pairs of BCa samples and screened for circRNAs. CircRNAs, microRNAs (miRNAs) and mRNAs, as well as levels of P27 and P21, in human cells and tissues were detected by qRT-PCR and western blot, respectively. CircRNA-miRNA interactions and miRNA-downstream mRNAs interactions were investigated by RNA pull-down assay and fluorescence in situ hybridization (FISH) or luciferase reporter assays, respectively. Then, the function of circFAM114A2 in BCa was explored using cell proliferation, cell cycle and tumorigenesis assays in nude mice. Finally, the function of circFAM114A2 in cisplatin chemo-sensitivity in BCa was detected by IC50 and tumor formation of xenograft in cisplatin-treated nude mice. Results: We discovered that circFAM114A2 levels were decreased in BCa cell lines and tissues. According to follow-up data, BCa patients with higher circFAM114A2 expression had better survival. Importantly, the levels of circFAM114A2 were associated with the histological grade of BCa. Overexpression of circFAM114A2 inhibited cell proliferation and increased sensitivity to cisplatin chemotherapy. Mechanistically, circFAM114A2 directly sponged miR-222-3p/miR-146a-5p and subsequently influenced the expression of the downstream target genes P27/P21, which, in turn, inhibited progression of BCa.Conclusions: CircFAM114A2 acted as a tumor suppressor through a novel circFAM114A2/miR-222-3p/P27 and circFAM114A2/miR-146a-5p/P21 pathway. CircFAM1142 has therefore great potential as a prognostic biomarker and therapeutic target for BCa.

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CircFAM114A2 Promotes Cisplatin Sensitivity via miR-222-3p/P27 and miR-146a-5p/P21 Cascades in Urothelial Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.659166 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jiancheng Lv ◽

Zijian Zhou ◽

Jingzi Wang ◽

Xiao Yang ◽

Hao Yu ◽

...

Keyword(s):

Cell Proliferation ◽

Urothelial Carcinoma ◽

Target Genes ◽

Histological Grade ◽

Chemotherapy Resistance ◽

Circular Rnas ◽

Downstream Target ◽

Carcinoma Cell Lines ◽

Apoptosis Assay ◽

Cisplatin Sensitivity

IntroductionCircular RNAs (circRNAs) are non-coding RNAs that have the structure of a covalently closed loop. Increasing data have proven that circRNAs can influence the progression and chemotherapy sensitivity of tumors. Therefore, the underlying function and mechanisms of more circRNAs in progression and chemotherapy resistance are important.MethodsWe conducted RNA sequencing on five pairs of urothelial carcinoma samples and screened for circRNAs. CircFAM114A2 was found to be low expressed in urothelial carcinoma. The functions of circFAM114A2 in urothelial carcinoma were explored by cell cycle assay, IC50 determination assay, cell proliferation assay, apoptosis assay, and tumorigenesis assay.ResultsWe discovered that the levels of circFAM114A2 were decreased in urothelial carcinoma cell lines and tissues. According to follow-up data, urothelial carcinoma patients with higher circFAM114A2 expression had better survival. Importantly, the levels of circFAM114A2 were associated with the histological grade of urothelial carcinoma. CircFAM114A2 could inhibit cell proliferation and block more urothelial carcinoma cells in the G1 phase and then increase the sensitivity of urothelial carcinoma to cisplatin chemotherapy. Mechanistically, circFAM114A2 directly sponged miR-222-3p/miR-146a-5p and subsequently influenced the expressions of the downstream target genes P27/P21, which, in turn, inhibited the progression of urothelial carcinoma and increased the sensitivity of cancer cells to cisplatin chemotherapy.ConclusionCircFAM114A2 could inhibit progression and promote cisplatin sensitivity in urothelial carcinoma through novel circFAM114A2/miR-222-3p/P27 and circFAM114A2/miR-146a-5p/P21 pathways. CircFAM1142 has therefore great potential as a prognostic biomarker and therapeutic target for urothelial carcinoma.

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Sevoflurane inhibits malignant progression of colorectal cancer via hsa_circ_0000231-mediated miR-622

Journal of Biological Research-Thessaloniki ◽

10.1186/s40709-021-00145-6 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Jingpeng Wang ◽

Shuyuan Li ◽

Gaofeng Zhang ◽

Huihua Han

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cell Apoptosis ◽

Volatile Anesthetic ◽

Tumor Formation ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas

Abstract Background Sevoflurane (Sev), a commonly used volatile anesthetic, has been reported to inhibit the process of colorectal cancer (CRC). Circular RNAs (circRNAs) are revealed to participate in the pathogenesis of CRC. This study aims to reveal the mechanism of hsa_circ_0000231 in Sev-mediated CRC progression. Methods The expression of hsa_circ_0000231 and microRNA-622 (miR-622) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was determined by western blot analysis. Cell proliferation was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell colony formation and DNA content quantitation assays. Cell apoptosis was detected by Annexin V-fluorescein isothiocyanate and propidium iodide double staining and caspase 3 activity assays. Cell migration and invasion were investigated by wound-healing and transwell invasion assays, respectively. The putative relationship between hsa_circ_0000231 and miR-622 was predicted by circular RNA Interactome online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of hsa_circ_0000231 on Sev-mediated tumor formation in vivo were presented by in vivo assay. Results Hsa_circ_0000231 expression was upregulated, while miR-622 was downregulated in CRC tissues and cells compared with control groups. Sev treatment decreased hsa_circ_0000231 expression, but increased miR-622 expression in CRC cells. Sev treatment suppressed cell proliferation, migration and invasion, and induced cell apoptosis. Hsa_circ_0000231 overexpression restored Sev-mediated CRC progression in vitro. Additionally, hsa_circ_0000231 acted as a sponge of miR-622, and miR-622 inhibitors reversed the impacts of hsa_circ_0000231 silencing on CRC process. Furthermore, Sev treatment inhibited tumor growth by regulating hsa_circ_0000231 in vivo. Conclusion Hsa_circ_0000231 attenuated Sev-aroused repression impacts on CRC development by sponging miR-622. This findings may provide an appropriate anesthetic protocol for CRC sufferers undergoing surgery.

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Circ_0001421 facilitates glycolysis and lung cancer development by regulating miR-4677-3p/CDCA3

Diagnostic Pathology ◽

10.1186/s13000-020-01048-1 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Koudong Zhang ◽

Hang Hu ◽

Juan Xu ◽

Limin Qiu ◽

Haitao Chen ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Tumor Progression ◽

Lactate Production ◽

Tumor Formation ◽

Luciferase Reporter ◽

Circular Rnas ◽

Glucose Assay

Abstract Background Lung cancer (LC) is a malignant tumor originating in the bronchial mucosa or gland of the lung. Circular RNAs (circRNAs) are proved to be key regulators of tumor progression. However, the regulatory effect of circ_0001421 on lung cancer tumorigenesis remains unclear. Methods The expression levels of circ_0001421, microRNA-4677-3p (miR-4677-3p) and cell division cycle associated 3 (CDCA3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Methyl thiazolyl tetrazolium (MTT), Transwell and Tumor formation assays were performed to explore the role of circ_0001421 in LC. Glucose consumption and lactate production were examined by a Glucose assay kit and a Lactic Acid assay kit. Western blot was utilized to examine the protein levels of Hexokinase 2 (HK2) and CDCA3. The interaction between miR-4677-3p and circ_0001421 or CDCA3 was confirmed by dual-luciferase reporter assay. Results Circ_0001421 was increased in LC tissues and cells, and knockdown of circ_0001421 repressed cell proliferation, migration, invasion and glycolysis in vitro. Meanwhile, circ_0001421 knockdown inhibited LC tumor growth in vivo. Mechanistically, circ_0001421 could bind to miR-4677-3p, and CDCA3 was a target of miR-4677-3p. Rescue assays manifested that silencing miR-4677-3p or CDCA3 overexpression reversed circ_0001421 knockdown-mediated suppression on cell proliferation, migration, invasion and glycolysis in LC cells. Conclusion Circ_0001421 promoted cell proliferation, migration, invasion and glycolysis in LC by regulating the miR-4677-3p/CDCA3 axis, which providing a new mechanism for LC tumor progression.

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Hsa_Circular RNA_0001013 Exerts Oncogenice Effects in Gastric Cancer Via the microRNA-136/TWSG1 Axis

10.21203/rs.3.rs-1012547/v2 ◽

2022 ◽

Author(s):

Zhaofeng Gao ◽

Lingyu Hu ◽

Fei Chen ◽

Chunhua He ◽

Biwen Hu ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Tumor Growth ◽

Microarray Analysis ◽

Nude Mice ◽

Critical Role ◽

Luciferase Reporter ◽

Clinical Samples ◽

Circular Rnas

Abstract Background：Gastric cancer (GC) is one of the most principle malignant cancers in the digestive system. Moreover, the critical role of circular RNAs (circRNAs) has been identified in GC development. Methods：In this context, the purpose of research was to explore the regulatory mechanism circ_0001013, a novel circRNAs predicted by our research, in GC. The differential circRNAs and related mechanism in GC were predicted by microarray analysis. Circ_0001013, miR-136, and TWSG1 expression in GC clinical samples and cells was detected by RT-qPCR. The relationship among circ_0001013, miR-136, and TWSG was assessed by dual-luciferase reporter assay, biotin coupled probe pull-down assay, and biotin coupled miRNA capture. After gain- and loss-of-function assays in GC cells, cell proliferation, migration, invasion, and cell cycle and apoptosis were measured by EdU assay, scratch test, Transwell assay, and flow cytometry respectively. The effect of circ_0001013 on tumor growth was detected by xenograft tumor in nude mice. Results ：Microarray analysis predicted a novel circRNA, circ_0001013, was upregulated in GC, which was confirmed by RT-qPCR detection in GC tissues and cells. Besides, miR-136 was downregulated but TWSG1 was highly expressed in GC tissues. Mechanically, circ_0001013 could bind to miR-136, and miR-136 negatively targeted TWSG1 in GC cells. Silencing circ_0001013 or TWSG1 or overexpressing miR-136 decreased GC cell proliferation, migration, invasion, and cell cycle arrest and accelerated cell apoptosis. Circ_0001013 silencing decreased TWSG1 expression and inhibited transplanted tumor growth in nude mice. Conclusion：Circ_0001013 elevated TWSG1 expression by binding to miR-136, thereby exerting oncogenic effect in GC.

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Hsa_Circular RNA_0001013 Exerts Oncogenice Effects in Gastric Cancer via the MicroRNA-136/TWSG1 Axis

10.21203/rs.3.rs-1012547/v1 ◽

2021 ◽

Author(s):

Zhaofeng Gao ◽

Lingyu Hu ◽

Fei Chen ◽

Chunhua He ◽

Biwen Hu ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Tumor Growth ◽

Microarray Analysis ◽

Nude Mice ◽

Critical Role ◽

Luciferase Reporter ◽

Clinical Samples ◽

Circular Rnas

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Hsa_circRNA_103124 Upregulation in Crohn’s Disease Promotes Cell Proliferation and Inhibits Autophagy by Regulating the Hsa-miR-650/AKT2 Signaling Pathway

Frontiers in Genetics ◽

10.3389/fgene.2021.753161 ◽

2021 ◽

Vol 12 ◽

Author(s):

Juan Yin ◽

Fuyi Tong ◽

Yulan Ye ◽

Tong Hu ◽

Lijuan Xu ◽

...

Keyword(s):

Cell Proliferation ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Signaling Pathway ◽

Luciferase Reporter ◽

Circular Rnas ◽

Downstream Target ◽

Reverse Transcription Pcr ◽

Reporter Assays ◽

Pathway Analyses

Circular RNAs (circRNAs) play important roles in the pathogenesis of Crohn’s disease (CD). We discovered that hsa_circRNA_103124 was upregulated in CD patients in our previous study. Nonetheless, the function of hsa_circRNA_103124 is unclear. In this study, hsa_circRNA_103124 was predicted to interact with hsa-miR-650. Gene Ontology (GO) and pathway analyses identified AKT serine/threonine kinase 2 (AKT2) as the downstream target protein of hsa-miR-650. Activated AKT2 inhibits autophagy, but promotes cell proliferation. Recent studies suggest that the inhibition of autophagy is one of the mechanisms of CD pathogenesis. Therefore, we inferred that hsa_circRNA_103124 might regulate autophagy and proliferation by targeting AKT2 as a sponge for hsa-miR-650. Here, quantitative reverse transcription PCR (RT-QPCR) results revealed that upregulated hsa_circRNA_103124 expression in patients with CD was negatively correlated with hsa-miR-650 expression but positively correlated with the white blood cell count and calprotectin levels. TSC complex subunit 1 (TSC1), one of the proteins upstream of autophagy was downregulated in patients with CD. Consisting with the bioinformatics prediction, it was verified that hsa_circRNA_103124 targeted to hsa-miR650 by fluorescence in situ hybridization (FISH) and luciferase reporter assays. A hsa-miR-650 inhibitor reversed the promotion of rapamycin-induced autophagy and the inhibition of cell proliferation by the hsa_circRNA_103124 siRNA. However, hsa-miR-650 mimics reversed the inhibition of rapamycin-induced autophagy and the promotion of cell proliferation through hsa_circRNA_103124 overexpression. These results indicate that hsa_circRNA_103124 upregulation in patients with CD promotes cell proliferation and inhibits autophagy by regulating the hsa-miR-650/AKT2 signaling pathway.

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LncRNA MAFG-AS1 Promotes the Progression of Bladder Cancer by Targeting the miR-143-3p/COX-2 Axis

Pathobiology ◽

10.1159/000509957 ◽

2020 ◽

Vol 87 (6) ◽

pp. 345-355

Author(s):

Dengbao Li ◽

Siwen Zhong ◽

Zhiqiang Zhu ◽

Xinan Jiang ◽

Junhao Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cell Lines ◽

Biological Effects ◽

Histological Grade ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Cox 2 ◽

Regulatory Effects

Background: Long noncoding RNAs (lncRNAs) are potential biomarkers that are very important for the development of cancer. Studies show that lncRNAs are significantly correlated with the carcinogenesis and progression of bladder cancer (BLCA). In this research, we aimed at probing into the role of lncRNA MAFG-AS1 in the tumorigenesis of BLCA. Methods: RT-qPCR was employed to detect MAFG-AS1 expression in BLCA tissues and cells. MAFG-AS1 siRNA and overexpression plasmid were transfected into 5637 and T24 BLCA cell lines to inhibit or upregulate MAFG-AS1 expression, respectively, and then the regulatory functions of MAFG-AS1 on BLCA cell proliferation, migration, and invasion were assessed using cell counting kit-8 (CCK-8) assay, EdU method, and Transwell experiments, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation were conducted to validate the targeting relationships between MAFG-AS1 and miR-143-3p, and miR-143-3p and COX-2. In addition, miR-143-3p was repressed in MAFG-AS1-silenced 5637 and T24 cell lines, and the function of MAFG-AS1/miR-143-3p axis in BLCA cells was further evaluated. The regulatory effects of MAFG-AS1 and miR-143-3p on the expression of COX-2 protein were detected by Western blot. Results: MAFG-AS1 was remarkably upregulated in BLCA patient tissues and cell lines, and its high expression was closely related to histological grade, tumor size, and lymph node metastasis. Silencing of MAFG-AS1 inhibited BLCA cell proliferation, metastasis, and invasion, while overexpression of MAFG-AS1 in BLCA cells had opposite biological effects. MAFG-AS1 was proved to target miR-143-3p to repress its expression. Moreover, it was confirmed that MAFG-AS1 and miR-143-3p could modulate COX-2 expression. Conclusion: The MAFG-AS1/miR-143-3p/COX-2 axis contributes to BLCA progression.

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Circular RNA circ-ZKSCAN1 inhibits bladder cancer progression through miR-1178-3p/p21 axis and acts as a prognostic factor of recurrence

Molecular Cancer ◽

10.1186/s12943-019-1060-9 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 22

Author(s):

Junming Bi ◽

Hongwei Liu ◽

Wei Dong ◽

Weibin Xie ◽

Qingqing He ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Progression ◽

Tumor Grade ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Rank Test ◽

Circular Rnas

Abstract Background Circular RNAs (circRNAs) represent a subclass of regulatory RNAs that have been shown to have significant regulatory roles in cancer progression. However, the biological functions of circRNAs in bladder cancer (BCa) are largely unknown. Methods Cell invasion models were established, and invasion-related circRNAs were detected by qPCR. Using above method, circ-ZKSCAN1 was picked out for further study. Circ-ZKSCAN1 expression and survival analyses were performed through qPCR. The survival curves were generated by the Kaplan-Meier method, and the log-rank test was used to assess the significance. Cell proliferation, migration and invasion were examined to investigate the function of circ-ZKSCAN1. Tumorigenesis in nude mice was assessed to determine the effect of circ-ZKSCAN1 in bladder cancer. Biotin-coupled probe pull-down assays, FISH and luciferase reporter assays were conducted to confirm the relationship between circ-ZKSCAN1 and microRNA. RNA-seq revealed different molecular changes in downstream genes. Results Here, we found that circ-ZKSCAN1 was downregulated in BCa tissues and cell lines. Circ-ZKSCAN1 levels were associated with survival, tumor grade, pathological T stage and tumor recurrence. Overexpressed circ-ZKSCAN1 inhibits cell proliferation, migration, invasion and metastasis in vitro and in vivo. Mechanistically, we demonstrated that circ-ZKSCAN1 upregulated p21 expression by sponging miR-1178-3p, which suppressed the aggressive biological behaviors in bladder cancer. Conclusions These results reveal that Circ-ZKSCAN1 acts as a tumor suppressor via a novel circ-ZKSCAN1/miR-1178-3p/p21 axis, which have the important role in the proliferation, migration and invasion ablitities of BCa cells and provide a novel perspective on circRNAs in BCa progression.

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Hsa-miR-557 Inhibits Osteosarcoma Growth Through Targeting KRAS

Frontiers in Genetics ◽

10.3389/fgene.2021.789823 ◽

2022 ◽

Vol 12 ◽

Author(s):

Zhi Qiao ◽

Jinfeng Li ◽

Hongwei Kou ◽

Xiangrong Chen ◽

Deming Bao ◽

...

Keyword(s):

Cell Cycle ◽

Nude Mice ◽

Target Genes ◽

Tumor Formation ◽

Cell Cycle Analysis ◽

Luciferase Reporter ◽

Expression Of Genes ◽

Therapeutic Molecules

Objective: Osteosarcoma is the most common malignancy in the skeletal system; studies showed an important role of miRNAs in tumorigenesis, indicating miRNAs as possible therapeutic molecules. This study found abnormal hsa-miR-557 expression levels in osteosarcoma and tried to explore the potential function and the mechanism.Methods: Differential expression genes of osteosarcoma were analyzed using GSE28423 from the GEO database. Survival analysis of miRNAs was conducted with data obtained from the TARGET-OS database. STRING and miRDIP were used to predict target genes of hsa-miR-557; KRAS was then verified using dual-luciferase reporter assay. Expression of genes was detected by qPCR, and levels of proteins were detected by Western blot. The proliferation ability of cells was detected by CCK-8 and cell cycle analysis. Tumor formation assay in nude mice was used to detect the influence of osteosarcoma by hsa-miR-557 in vivo.Results: Analysis from the GEO and TARGET databases found 12 miRNAs that are significantly related to the osteosarcoma prognosis, 7 downregulated (hsa-miR-140-3p, hsa-miR-564, hsa-miR-765, hsa-miR-1224-5p, hsa-miR-95, hsa-miR-940, and hsa-miR-557) and 5 upregulated (hsa-miR-362-3p, hsa-miR-149, hsa-miR-96, hsa-miR-744, and hsa-miR-769-5p). CCK-8 analysis and cell cycle analysis found that hsa-miR-557 could significantly inhibit the proliferation of osteosarcoma cells. The tumor formation assay in nude mice showed that tumor sizes and weights were inhibited by hsa-miR-557 transfection. Further studies also proved that hsa-miR-557 could target the 3′UTR of KRAS and modulate phosphorylation of downstream proteins.Conclusion: This study showed that hsa-miR-557 could inhibit osteosarcoma growth both in vivo and in vitro, by modulating KRAS expression.

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