miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

Mikó, Edit; Margitai, Zoltán; Czimmerer, Zsolt; Várkonyi, Ildikó; Dezső, Balázs; Lányi, Árpád; Bacsó, Zsolt; Scholtz, Beáta

doi:10.1016/j.febslet.2011.03.039

Cited by 123 publications

(86 citation statements)

References 25 publications

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“…Gene expression in cancer is regulated by oncogenes and tumor suppressor genes. In recent years, with the identification of microRNAs (miRNAs) and their functions, Li et al (20) and Miko et al (21) reported that PLK2 was a target gene of miR126. miRNAs are a type of small non-coding RNA, ~22-nucleotides, which downregulate the translation of target mRNAs (22,23).…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Thus, PLK2 seems to inhibit oncogenic transformation (26). A previous study showed that PLK2 is a target gene of miR-126 (21,27), which is also as a tumor suppressor (12). However, the inhibitory effects of a specific miRNA on a target gene appear to be cell type-specific.…”

Section: Mir-126 Inhibits Growth Of Sgc-7901 Cells By Synergisticallymentioning

confidence: 99%

“…To date, the target genes of miR-126 that have been confirmed are PI3KR2 (18), IRS-1 (19), Crk (12), SOX2 (13), ADAM9, MMP7 (20) and SCL7A5 (21). Except for SOX2, which is a tumor suppressor, other genes are involved in tumor formation and progression.…”

Section: Mir-126 Inhibits Growth Of Sgc-7901 Cells By Synergisticallymentioning

confidence: 99%

“…However, the inhibitory effects of a specific miRNA on a target gene appear to be cell type-specific. For example, miR-126 overexpression does not suppress PLK2 expression in SCLC cells (21). TOM1 is a target gene of miR-126 in cystic fibrosis (CF) airway epithelium cells, but not in MCF7 cells (28).…”

Section: Mir-126 Inhibits Growth Of Sgc-7901 Cells By Synergisticallymentioning

confidence: 99%

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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

Liu

Wang

Zhao

et al. 2014

International Journal of Oncology

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Abstract. MicroRNA (miRNA)-126 (miR-126) was reported to be downregulated and to act as a tumor suppressor in cancers of the lung, cervix, bladder and prostate. However, the functions of miR-126 in gastric cancer appear to be diverse and are largely unknown. MiR-126 was reported to act as a tumor suppressor by targeting the Crk gene, or as an oncogene by targeting the SOX2 gene in gastric cancer. We identified that the expression of miR-126 was decreased in gastric cancer cell lines and tissues. PLK2, a tumor suppressor gene, was directly regulated by miR-126 in SGC-7901 cells. Overexpression of miR-126 not only suppressed the growth and clone formation of SGC-7901 cells, but also induced apoptosis in vitro, whereas inhibition of miR-126 slightly promoted SGC-7901 cell proliferation. The cell cycle was not affected by miR-126. Moreover, miR-126 suppressed tumor growth in vivo in a xenograft model. PLK2, PI3KR2and Crk were regulated by miR-126 in SGC-7901 cells. We infer that the functions of miR-126 in gastric cancer depend on synergistic targeting balance between oncogenes and anti-oncogenes. Our study indicates that miR-126 is a tumor suppressor, which in the future may become a therapeutic target for gastric cancer.

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“…It has been confirmed that miRNAs regulate many tumor-related processes including proliferation, migration, and invasion [5]. Accumulating studies has revealed that dysregulation of miRNAs occurs in various human malignancies, including GC [6,7]. Among these miRNAs, miR-339 was reported to be deregulated in breast and colorectal cancer [8,9].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐339, an epigenetic modulating target is involved in human gastric carcinogenesis through targeting NOVA1

Shen

Zhang

et al. 2015

FEBS Letters

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a b s t r a c tThe role of miR-339 in human gastric cancer (GC) remains unclear. Here, we found that miR-339 is remarkably decreased in primary GC tissues. Overexpression of miR-339 in GC cells significantly suppressed proliferation, migration, invasion, and tumorigenicity. Furthermore, NOVA1 was confirmed as a target of miR-339. Restoration of NOVA1 in miR-339-overexpressing GC cells partially impaired the inhibitory effects of miR-339. More importantly, epigenetic modification may be involved in the modulation of miR-339 expression. These findings uncover a novel role for miR-339 in gastric carcinogenesis, and restoration of miR-339 could be considered as a potential therapeutic strategy for GC treatment.

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miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

Cited by 123 publications

References 25 publications

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

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

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

MicroRNA‐339, an epigenetic modulating target is involved in human gastric carcinogenesis through targeting NOVA1

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