Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B

Lin, Kai-Ti; Yeh, Yu-Ming; Chuang, Chi-Mu; Yang, Scarlett Y; Chang, Jui-Chi; Sun, Shaoli; Wang, Yi-Shiang; Chao, Kuan-Chong; Wang, Lu‐Hai

doi:10.1038/ncomms6917

Cited by 94 publications

(122 citation statements)

References 43 publications

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“…The A2b-Epac1-Rap1B Pathway in the Context of Migration of Cancer Cells-Our discovery of a critical involvement of Rap1B in the positioning of the centrosome and nucleus may explain previous observations that cells isolated from Rap1B-deficient mice display decreased migration (80), that Rap1B knockdown results in impaired cell migration of human endothelial cells (81), and that Rap1B suppression by miR-708 results in inhibition of ovarian cancer cell migration/invasion (83). However, some studies reported a correlation between hypoxia and cell motility in cancer cells, including enhanced metastatic potential (84,85).…”

Section: Discussionmentioning

confidence: 97%

Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration

Chan

Zuo

et al. 2016

Journal of Biological Chemistry

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The tight, relative positioning of the nucleus and centrosome in mammalian cells is important for the regulation of cell migration. Under pathophysiological conditions, the purinergic A2b receptor can regulate cell motility, but the underlying mechanism remains unknown. Expression of A2b, normally low, is increased in tissues experiencing adverse physiological conditions, including hypoxia and inflammation. ATP is released from such cells. We investigated whether extracellular cues can regulate centrosome-nucleus positioning and cell migration. We discovered that hypoxia as well as extracellular ATP cause a reversible increase in the distance between the centrosome and nucleus and reduced cell motility. We uncovered the underlying pathway: both treatments act through the A2b receptor and specifically activate the Epac1/RapGef3 pathway. We show that cells lacking A2b do not respond in this manner to hypoxia or ATP but transfection of A2b restores this response, that Epac1 is critically involved, and that Rap1B is important for the relative positioning of the centrosome and nucleus. Our results represent, to our knowledge, the first report demonstrating that pathophysiological conditions can impact the distance between the centrosome and nucleus. Furthermore, we identify the A2b receptor as a central player in this process.

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Section: Discussionmentioning

confidence: 97%

Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration

Chan

Zuo

et al. 2016

Journal of Biological Chemistry

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“…The number and size of tumor nodules in the peritoneal cavity as well as the volume of ascites fluid were reduced with transfectants in comparison to the control cell line (79). (86). GC are used in conjunction with chemotherapy of EOC to prevent hypersensitivity reactions (87).…”

Section: Mir-138mentioning

confidence: 99%

“…GC are used in conjunction with chemotherapy of EOC to prevent hypersensitivity reactions (87). miR-708 is down-regulated in metastatic OVC and patients with high miR-708 expression show significantly better survival (86). miR-708 inhibits migration and invasion of EOC cell lines as shown by wound healing and transwell Boyden chamber assays (86).…”

Section: Mir-138mentioning

confidence: 99%

“…miR-708 is down-regulated in metastatic OVC and patients with high miR-708 expression show significantly better survival (86). miR-708 inhibits migration and invasion of EOC cell lines as shown by wound healing and transwell Boyden chamber assays (86). Ras-related protein-1B (Rap-1B), a small GTPase, was identified as a direct target of miR-708 (Figure 2) (86).…”

Section: Mir-138mentioning

confidence: 99%

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Potential microRNA-related Targets for Therapeutic Intervention with Ovarian Cancer Metastasis

Weidle

Birzele

Kollmorgen

et al. 2018

CGP

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“…Ovarian cancer is one of the most frequent malignancies of the female reproductive system, with an incidence rate of ~3% (1), and is the sixth most common type of cancer in women (2). However, the mortality rate associated with ovarian cancer is the highest of the gynecological malignancies.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of S100A14 in human serous ovarian carcinoma

et al. 2015

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Abstract. S100 calcium binding protein A14 (S100A14) is a member of the S100 protein family that plays an important role in the progression of several types of cancer. In the present study, the expression and clinical effect of S100A14 was evaluated in serous ovarian carcinoma (SOC). SOC tissue specimens and a panel of normal ovarian and fallopian tubal tissue specimens were obtained between November 2008 and August 2012 from the Affiliated Hospital of Qingdao University. Immunohistochemistry (IHC) was used to detect the expression of S100A14 in the SOC and normal control tissues. In addition, ELISA was performed to assess S100A14 expression in a subset of serum samples. The association between the expression of S100A14 in SOC and the corresponding clinical and pathological data was analyzed. The IHC results revealed that S100A14 was mainly located in the cytoplasm of the majority of SOC cells, and the expression levels of S100A14 in the tumor tissues were significantly increased compared with the levels identified in normal ovarian specimens (P<0.001). Consistently, the serum levels of S100A14 in patients with SOC were also increased compared with the levels in healthy individuals (P<0.001). S100A14 expression was similar in the epithelium of SOC lesions and the fallopian tube, which supported the dualistic model for ovarian serous carcinogenesis. Additional analysis of the expression of S100A14 and corresponding clinical and pathological data revealed the correlation between the elevated expression of S100A14 and resistance to platinum-based chemotherapy. However, the protein level of S100A14 was not associated with the pathological stage, differentiation or metastasis of SOC. Overall, the present results demonstrate that S100A14 is likely to be involved in the resistance of SOC to platinum-based chemotherapy.

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Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B

Cited by 94 publications

References 43 publications

Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration

Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration

Potential microRNA-related Targets for Therapeutic Intervention with Ovarian Cancer Metastasis

Overexpression of S100A14 in human serous ovarian carcinoma

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