MicroRNA-146a is down-regulated in gastric cancer and regulates cell proliferation and apoptosis

Hou, Zhibo; Xie, Li; Yu, Lan; Qian, Xiaoping; Liu, Baorui

doi:10.1007/s12032-011-9862-7

Cited by 82 publications

(60 citation statements)

References 23 publications

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“…This result is consistent with a demonstrated role of miR-146a in other cancers, such as pancreatic and breast cancers, where it inhibits cancer progression and invasion (8,26,33). A recent report also showed a positive correlation of miR-146a expression with the survival time of gastric cancer patients (25). Furthermore, the overexpression of miR-146a inhibits the proliferation and survival of breast, prostate, and pancreatic cancer cells through the downregulation of other targets in these cells, including ROCK1, EGFR, and MTA-2 (8,33,34).…”

Section: Discussionsupporting

confidence: 90%

MicroRNA-146a Inhibits Glioma Development by Targeting Notch1

Mei

Bachoo²,

Zhang³

2011

Molecular and Cellular Biology

158

131

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Dysregulated epidermal growth factor receptor (EGFR) signaling through either genomic amplification or dominant-active mutation (EGFR vIII ), in combination with the dual inactivation of INK4A/ARF and PTEN, is a leading cause of gliomagenesis. Our global expression analysis for microRNAs revealed that EGFR activation induces miR-146a expression, which is further potentiated by inactivation of PTEN. Unexpectedly, overexpression of miR-146a attenuates the proliferation, migration, and tumorigenic potential of Ink4a/Arf ؊/؊ Pten ؊/؊ Egfr vIII murine astrocytes. Its ectopic expression also inhibits the glioma development of a human glioblastoma cell line in an orthotopic xenograft model. Such an inhibitory function of miR-146a on gliomas is largely through downregulation of Notch1, which plays a key role in neural stem cell maintenance and is a direct target of miR-146a. Accordingly, miR-146a modulates neural stem cell proliferation and differentiation and reduces the formation and migration of glioma stem-like cells. Conversely, knockdown of miR-146a by microRNA sponge upregulates Notch1 and promotes tumorigenesis of malignant astrocytes. These findings indicate that, in response to oncogenic cues, miR-146a is induced as a negative-feedback mechanism to restrict tumor growth by repressing Notch1. Our results provide novel insights into the signaling pathways that link neural stem cells to gliomagenesis and may lead to new strategies for treating brain tumors.Gliomas are the most frequently observed brain tumors, with glioblastoma multiforme (GBM) being the most common and aggressive form in adults (35). Despite major therapeutic improvements made by combining neurosurgery, chemotherapy, and radiotherapy, the prognosis and survival rate for patients with GBM is still extremely poor (7). The deadly nature of GBM originates from explosive growth and invasive behavior, which are fueled by dysregulation of multiple signaling pathways. Epidermal growth factor receptor (EGFR) activation, in cooperation with loss of tumor suppressor functions, such as mutations in Ink4a/Arf and Pten genes, constitutes a lesion signature for GBM (4). Such dysregulated genetic pathways are sufficient to transform neural stem cells (NSCs) or astrocytes into cancer stem-like cells. This gives rise to highgrade malignant gliomas with a pathological phenotype resembling human GBM (5, 59). However, the downstream events underlying these genetic dysregulations in gliomagenic cells have not been fully elucidated.MicroRNAs are 20-to 22-nucleotide noncoding RNA molecules that have emerged as key players in controlling NSC self-renewal and differentiation (11,57). Aberrant expression of miRNAs, such as miR-21, miR-124, and miR-137, is linked to glioma formation (49). miR-199b-5p and miR-34a impair cancer stem-like cells through the negative regulation of several components of the Notch pathway in brain tumors (18,21). The Notch pathway is an evolutionarily conserved signaling pathway that plays an important role in neurogenesis (3, 10, 23). Upon bindi...

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Section: Discussionsupporting

confidence: 90%

MicroRNA-146a Inhibits Glioma Development by Targeting Notch1

Mei

Bachoo²,

Zhang³

2011

Molecular and Cellular Biology

158

131

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“…In addition, Kim et al (11) also indicated enhanced miR-146a level in gastric cancer. However, recently, Hou et al (28) reported different expression of miR-146a in gastric cancer tissues. They found that 36 of 43 gastric cancer tissue samples (84%) showed decreased expression of miR-146a.…”

Section: Discussionmentioning

confidence: 99%

Increased miR-146a in gastric cancer directly targets SMAD4 and is involved in modulating cell proliferation and apoptosis

Xiao

Zhu²,

Li³

et al. 2011

Oncol Rep

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“…Gastric cancer (GC) is the second cause of cancerassociated death and the fourth most widespread tumor worldwide [4,5]. The development of GC involves various factors, including oncogenes and tumor suppressors.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-204-5p inhibits gastric cancer cell proliferation by downregulating USP47 and RAB22A

Zhang

Yin

et al. 2014

Med Oncol

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MicroRNAs (miRNAs) are a type of small noncoding RNAs that are strongly implicated in carcinogenesis. However, the potential diagnostic, prognostic and therapeutic roles of the majority of miRNAs in the pathological processes of tumorigenesis remain largely unknown. Our and others' data revealed that miR-204-5p was significantly downregulated in gastrointestinal tumor tissues compared with adjacent noncancerous tissues. The downregulation of miR-204-5p was confirmed in our gastric cancer (GC) cohort, and we showed that ectopic expression of miR-204-5p inhibited, whereas silencing miR-204-5p expression promoted GC cell proliferation in vitro. Subsequent mechanistic investigations identified that USP47 and RAB22A are direct functional targets of miR-204-5p in GC. Silencing the expression of USP47 and RAB22A using siRNA phenocopied the proliferation-inhibiting function of miR-204-5p in GC cells. Our results uncovered that miR-204-5p acts as a tumor suppressor in GC through inhibiting USP47 and RAB22A.

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MicroRNA-146a is down-regulated in gastric cancer and regulates cell proliferation and apoptosis

Cited by 82 publications

References 23 publications

MicroRNA-146a Inhibits Glioma Development by Targeting Notch1

MicroRNA-146a Inhibits Glioma Development by Targeting Notch1

Increased miR-146a in gastric cancer directly targets SMAD4 and is involved in modulating cell proliferation and apoptosis

MicroRNA-204-5p inhibits gastric cancer cell proliferation by downregulating USP47 and RAB22A

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