MicroRNA-221 Induces Cell Survival and Cisplatin Resistance through PI3K/Akt Pathway in Human Osteosarcoma

Zhao, Guangyi; Cai, Chengkui; Yang, Tao; Qiu, Xiuchun; Liao, Bo; Li, Wei; Ji, Zhenwei; Zhao, Jian; Zhao, Haixia; Guo, Mingzhou; Ma, Qiang; Xiao, Chun; Fan, Qingyu; Ma, Baoan

doi:10.1371/journal.pone.0053906

Cited by 205 publications

(163 citation statements)

References 61 publications

(92 reference statements)

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“…A B OS cells. These findings are also concordant with those of previous studies, which indicated that the PI3K/Akt pathway has a critical role in cancer chemoresistance (22)(23)(24)(25). Of note, the selective PI3K inhibitor only blocked ~50% of the effect of PCX on cisplatin chemoresistance and cell survival in OS cells, suggesting the involvement of other signaling pathways, which may be identified in further studies.…”

Section: Discussionsupporting

confidence: 92%

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Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3-kinase signaling

Huang

et al. 2015

Molecular Medicine Reports

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Abstract. Osteosarcoma (OS) is the most common type of primary bone malignancy. The use of multiagent, intensive chemotherapy has markedly improved the long-term survival rate of patients with OS. However, chemoresistance continues to be the principal reason for poor survival and disease recurrence in patients with OS. Innate or acquired resistance to cisplatin, which is one of the most effective drugs against OS, is common. Understanding the molecular basis underlying cisplatin chemoresistance in OS cells may serve as a basis for the identification of novel therapeutic targets and biomarkers. High expression levels of podocalyxin (PCX) have been shown to be correlated with poor outcome in various types of cancer. A recent study suggested that PCX may contribute to cancer chemoresistance. The present study aimed to explore the role of PCX in OS by determining its effects on cisplatin chemoresistance in OS cells. Stable overexpression and knockdown of PCX were performed in MG-63 and U2OS human OS cell lines. Overexpression of PCX in the two cell lines significantly increased the half maximal inhibitory concentration (IC 50 ) of cisplatin, cell colony formation, phosphatidylinositide 3-kinase (PI3K) activity and Akt phosphorylation at serine 473, and decreased cisplatin-induced cell apoptosis. Furthermore, the effects of PCX were largely attenuated by treatment with the selective PI3K inhibitor BKM120. Conversely, knockdown of PCX expression markedly decreased the IC 50 of cisplatin, cell colony formation, PI3K activity and Akt phosphorylation at serine 473, and increased cisplatin-induced cell apoptosis. In conclusion, the present study was the first, to the best of our knowledge, to provide evidence that PCX promotes cisplatin chemoresistance in OS cells through a PI3K-dependent mechanism. The results of the present study provided novel insight not only into the functional role of PCX in cancer, but also into the molecular mechanisms underlying OS chemoresistance.

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Section: Discussionsupporting

confidence: 92%

“…Previous studies have demonstrated that the PI3K/Akt pathway is important for cancer cell chemoresistance (22)(23)(24)(25). Therefore, the present study examined the effects of PCX on the activity of PI3K and phosphorylation of Akt in OS cells.…”

Section: Effects Of Pcx On Pi3k Activity and Phosphorylation Of Akt Imentioning

confidence: 95%

Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3-kinase signaling

Huang

et al. 2015

Molecular Medicine Reports

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“…miR, microRNA. phosphoinositide 3-kinase/Akt pathway (27). Furthermore, increased levels of miR-128 are negatively correlated with PTEN levels, and increased proliferation of MG63 and U2OS OS cells (28).…”

Section: Discussionmentioning

confidence: 97%

MicroRNA screening identifies circulating microRNAs as potential biomarkers for osteosarcoma

Li¹,

Zhang²,

Liu³

et al. 2015

Oncology Letters

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Abstract. MicroRNAs (miRNAs) are a family of small non-protein coding RNAs, which regulate the expression of a wide variety of genes at the post-transcriptional level to control numerous biological and pathological processes. Various circulating miRNAs have been identified as potential diagnostic and prognostic biomarkers in multiple types of cancer and disease. The aim of the present study was to identify potential miRNA biomarkers for the early diagnosis and relapse prediction of osteosarcoma (OS). miRNA profiling was performed on serum from patients with osteosarcoma and healthy controls. All putative miRNAs were verified by reverse transcription-quantitative polymerase chain reaction analysis of 20 pre-therapeutic OS patients and 20 healthy individuals. The expression of miR-106a-5p, miR16-5p, miR-20a-5p, miR-425-5p, miR451a, miR-25-3p and miR139-5p was demonstrated to be downregulated in the serum of OS patients when compared with that of the healthy controls. Receiver-operating characteristic curve analyses indicated that these 7 miRNAs may be used as diagnostic biomarkers with the ability to discriminate between the healthy cohort and patients with OS. These results provide novel insights into the use of miRNAs in early blood screening for OS.

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“…They negatively regulate gene expression through base-pairing to the 3'-untranslated region (UTR) of target messenger RNA (mRNA), resulting in the inhibition of translation and mRNA degradation (4,5). Beyond involvement in diverse biological processes, including cell growth, apoptosis, development, differentiation and endocrine homeostasis (6), emerging evidence indicates that the deregulation or dysfunction of miRNAs contribute to human carcinogenesis and cancer progression (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Decreased microRNA-132 and its function in human non-small cell lung cancer

Liu

Song

Pei

et al. 2015

Molecular Medicine Reports

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Abstract. has been shown to be dysregulated in certain types of human malignancies and is associated with tumor progression. However, its function in non-small cell lung cancer (NSCLC) and whether it is differentially expressed in this disease, remain unclear. Thus, the aim of the present study was to investigate the effects of miR-132 on NSCLC tumorigenesis and progression. Using reverse transcription-quantitative polymerase chain reaction, miR-132 expression was detected in NSCLC cell lines and primary tumor tissues. The association between miR-132 expression, and clinicopathological factors and prognosis was assessed using statistical analysis. An MTT assay, flow cytometry, Transwell invasion assays and scratch migration assays were conducted in order to examine the proliferation, apoptosis, invasion and migration of NSCLC cells that had been transfected with miR-132 mimics or inhibitors. The results showed that miR-132 expression levels were significantly downregulated in NSCLC cells compared with that in corresponding non-cancerous lung tissues (P<0.001). In addition, reduced miR-132 expression was significantly associated with lymph node metastasis (P=0.003), an advanced tumor-node-metastasis stage (P<0.001) and shorter overall survival (P<0.001). Multivariate regression analysis confirmed that downregulation of miR-132 was an independent predictor of prognosis. Furthermore, transfection of miR-132 mimics into the NSCLC cells reduced cell proliferation, invasion and migration, and promoted cell apoptosis. These findings indicate that miR-132 may be a novel diagnostic and prognostic marker, as well as a potential target for molecular therapy in NSCLC.

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MicroRNA-221 Induces Cell Survival and Cisplatin Resistance through PI3K/Akt Pathway in Human Osteosarcoma

Cited by 205 publications

References 61 publications

Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3-kinase signaling

Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3-kinase signaling

MicroRNA screening identifies circulating microRNAs as potential biomarkers for osteosarcoma

Decreased microRNA-132 and its function in human non-small cell lung cancer

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