miR-126 inhibits growth of SGC-7901 cells by synergistically targeting the oncogenes PI3KR2 and Crk, and the tumor suppressor PLK2

Liu, Li Ying; Wang, Wei; Zhao, Lin; Guo, Bo; Yang, Juan; Zhao, Xiao Ge; Hou, Ni; Ni, Lei; Wang, Ai Ying; Song, Tu Sheng; Huang, Chen; Xu, Jianrong

doi:10.3892/ijo.2014.2516

Cited by 44 publications

(41 citation statements)

References 35 publications

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“…The potential role of miR-126 in targeting the PIK3R2 -mediated PI3K/Akt signaling pathway was further evaluated. The luciferase reporter assay showed that PIK3R2 was a direct target of miR-126 in bladder cancer, which is consistent with previous evidence suggesting that PI3KR 2 is a target of miR-126 19,24…”

Section: Discussionsupporting

confidence: 90%

“…The invasive potential of bladder cancer cells can be attenuated with increased miR-126 levels by mechanistically targeting disintegrin and metalloproteinase domain-containing protein 9 17,18. By synergistically targeting oncogenes ( PI3KR2 and adaptor protein Crk ) and tumor suppressors ( polo-like kinase 2 ), miR-126 was shown to have an inhibitory effect on the growth of gastric cancer cell lines 19. Mechanistically, silencing miR-126 may alter the activation of the PI3K/Akt pathway, suggesting an important regulatory role for miR-126 in PI3K/Akt pathway transduction, which is considered to play a major role in bladder carcinogenesis 20,21.…”

Section: Introductionmentioning

confidence: 99%

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MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the <em>PIK3R2</em>-mediated PI3K/Akt signaling pathway

Xiao

Lin²,

Zhu

et al. 2016

OTT

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ObjectiveTo assess whether microRNA-126 (miR-126) targets phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2) and to determine the potential roles of miR-126 in regulating proliferation and invasion via the PIK3R2-mediated phosphatidylinositol 3 kinase (PI3K)-protein kinase B (Akt) signaling pathway in the human bladder BLS cell line.Materials and methodsA recombinant lentivirus (Lv) vector expressing miR-216 (Lv-miR-126) was successfully constructed, and Lv-miR-126 and Lv vector were transfected into the BLS cell line. A direct regulatory relationship between miR-126 and the PIK3R2 gene was demonstrated by luciferase reporter assays. To determine whether PIK3R2 directly participates in the miR-126-induced effects in BLS cells, anti-miR-126 and a PIK3R2 small interfering RNA (siRNA) were transfected into the BLS cells. Quantitative real-time polymerase chain reaction was used to measure miR-126 and PIK3R2 expressions. 5-Ethynyl-2′-deoxyuridine and colony formation assays to assess cell proliferation, flow cytometry for cell apoptosis and cell cycle analysis, Transwell assays for cell migration and invasion, and Western blots for PIK3R2, PI3K, phosphorylated PI3K (p-PI3K), Akt, and phosphorylated Akt (p-Akt) protein expressions were performed.ResultsLv-miR-126 significantly enhanced the relative expression of miR-126 in the BLS cells after infection (P<0.0001). MiR-126 overexpression inhibited the proliferation, cloning, migration, and invasion of BLS cells, promoted cell apoptosis, and induced S phase arrest (all P<0.05). PIK3R2, p-PI3K, and p-Akt protein expressions were significantly decreased in the BLS cells infected with Lv-miR-126. Luciferase assays showed that miR-126 significantly inhibited the PIK3R2 3′ untranslated region (3′UTR) luciferase reporter activity (P<0.05). The anti-miR-126 + PIK3R2 siRNA group had significantly decreased PIK3R2, p-PI3K, and p-Akt expressions compared with those of anti-miR-126 alone, as well as significantly decreased proliferation, invasion, and metastasis and increased apoptosis compared with the anti-miR-126 group (all P<0.05). Additionally, proliferation, invasion, and metastasis were significantly increased, and cell apoptosis was decreased compared with the PIK3R2 siRNA group (all P<0.05).ConclusionOverexpression of miR-126 negatively regulated the target gene PIK3R2 and further inhibited the PI3K/Akt signaling pathway, thereby inhibiting proliferation, migration, and invasion and promoting apoptosis in BLS cells.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the <em>PIK3R2</em>-mediated PI3K/Akt signaling pathway

Xiao

Lin²,

Zhu

et al. 2016

OTT

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“…It has been noted that miR-126 inhibits the invasion of gastric cancer cells partially by targeting v-crk avian sarcoma virus CT10 oncogene homolog (Crk) (30). Liu et al reported that miR-126 inhibits the growth of gastric cancer cells by targeting phosphoinositide 3-kinase regulatory subunit 2, Crk and polo-like kinase 2 (31). Thus, the present study expands on the understanding of the miR-126 targets and the function they serve in carcinogenesis.…”

Section: Discussionsupporting

confidence: 52%

MicroRNA-126 inhibits the migration and invasion of endometrial cancer cells by targeting insulin receptor substrate 1

Zhao

Zhu

et al. 2015

Oncology Letters

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Abstract. MicroRNAs (miRs) have been demonstrated to serve important roles in the development and progression of human cancer, primarily through the direct targeting of oncogenes or tumor suppressors. It has been previously suggested that miR-126 may be associated with endometrial cancer (EC). However, the exact role of miR-126 in the migration and invasion of EC cells has not yet been studied. The present study demonstrated that the expression of miR-126 was significantly decreased in EC tissues when compared with matched normal adjacent tissues. The current study reverse transcriptionquantitative polymerase chain reaction was performed in order to examine the expression level of miR-126. Wound healing and transwell assays were used to examine cell migration and invasion. A luciferase reporter assay was used to determine the targeting relationship and western blotting assay was performed to detect the protein expression. Furthermore, the overexpression of miR-126 significantly inhibited EC SKOV3 cell migration and invasion. Molecular mechanism investigation established that insulin receptor substrate 1 (IRS1) functioned as a direct miR-126 target, and its expression was negatively regulated by miR-126 at a post-transcriptional level in the SKOV3 cells. Additionally, the overexpression of IRS1 reversed the inhibitory effect of miR-126 overexpression on SKOV3 cell migration and invasion. In conclusion, the current study demonstrated that miR-126 inhibited EC cell migration and invasion, at least partially through the direct targeting of IRS1, suggesting that miR-126 may aid the treatment of EC metastasis.

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“…miR-126 is downregulated and acts as a tumor suppressor in stomach cancer (27). A previous study by our group also found that miR-126 acted as a tumor suppressor in gastric carcinoma, and PLK2 was a target gene of miR-126 (28). This therefore indicated that the upregulation of PLK2 in gastric cancer may be associated with the downregulation of miR-126; thus, miR-126 may also have a dominant role in gastric cancer.…”

Section: Discussionmentioning

confidence: 52%

Silencing of polo-like kinase 2 increases cell proliferation and decreases apoptosis in SGC-7901 gastric cancer cells

Liu

Wang

Zhao

et al. 2014

Molecular Medicine Reports

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Abstract. Polo-like kinase 2 (PLK2) is a serine/threonine protein kinase, which has vital roles during mitosis and the centrosome cycle. In acute myeloblastic leukemia and hepatocarcinogenesis, PLK2 acts as a tumor suppressor; however, the function of PLK2 in gastric cancer remains to be elucidated. In the present study, PLK2 was overexpressed in gastric cancer tissues and three types of gastric cancer cells, SGC-7901, MKN-45 and BGC-823. Transfection of SGC-7901 gastric cancer cells with small interfering (si)RNA against PLK2 exerted no effect on the ratio of cells at different stages of the cell cycle compared with that of the untransfected and control siRNA-transfected cells. In addition, silencing of PLK2 significantly enhanced the growth of SGC-7901 cells through inhibiting apoptosis. Furthermore, apoptosis-associated genes Bax and caspase 3 were found to be downregulated at the protein level. In conclusion, these results suggested that PLK2 may act as a tumor suppressor in gastric cancer, therefore indicating its therapeutic potential. IntroductionGastric cancer, also known as stomach cancer, has a high incidence rate in and is one of the most prominent causes of cancer-associated mortality in Asia (1). In addition, gastric cancer is the fourth most prevalent type of cancer worldwide and the second most frequent cause of cancer-associated mortality worldwide (2,3). The prognosis of gastric cancer patients is poor and it remains challenging to cure. Targeted gene therapy is a novel therapeutic approach for gastric cancer, for which the identification of tumor suppressors associated with this malignancy is essential.Polo-like kinase 2 (PLK2) is a member of the serine/threonine protein kinase family, which includes five members: PLK1, PLK2 (also termed SNK), PLK3 (also termed Fnk or Prk), PLK4 (also termed Sak) and PLK5 (4-6). These kinases have important roles during mitosis and the centrosome cycle (7). PLK2 is located in the centrosome and was found to be involved in embryonic development and cell cycle progression at the G 1 /S transition, as well as in skeletal development. Cell cycle analysis of cultured PLK2 -/-embryonic fibroblasts indicated that these cells proliferated more slowly than cells expressing PLK2 and exhibited delayed entry into S phase from G 1 (8). In central neurons, PLK2 was reported to be overexpressed in response to synaptic stimulation (9). Decreased expression of PLK2 was observed in B-cell malignancies; in addition, apoptosis was found to be induced in Burkitt's lymphoma cells through the ectopic expression of PLK2 (10). This therefore indicated that PLK2 may act as a tumor suppressor gene in hematologic malignancies (10,11). Pellegrino et al (12) showed that PLK2 was a tumor suppressor in hepatocarcinogenesis. In addition, Kothari et al (13) reported that PLK2 is an outlier kinase, which was highly expressed in Silencing of polo-like kinase 2 increases cell proliferation and decreases apoptosis in SGC-7901 gastric cancer cells

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miR-126 inhibits growth of SGC-7901 cells by synergistically targeting the oncogenes PI3KR2 and Crk, and the tumor suppressor PLK2

Cited by 44 publications

References 35 publications

MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the <em>PIK3R2</em>-mediated PI3K/Akt signaling pathway

MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the <em>PIK3R2</em>-mediated PI3K/Akt signaling pathway

MicroRNA-126 inhibits the migration and invasion of endometrial cancer cells by targeting insulin receptor substrate 1

Silencing of polo-like kinase 2 increases cell proliferation and decreases apoptosis in SGC-7901 gastric cancer cells

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