Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer

Chaluvally‐Raghavan, Pradeep; Jeong, Kang Jin; Pradeep, Sunila; Silva, Andreia; Yu, Shuangxing; Liu, Wenbin; Moss, Tyler J.; Rodríguez-Aguayo, Cristian; Zhang, Dong; Ram, Prahlad T.; Liu, Jinsong; Lu, Yiling; López-Berestein, Gabriel; Calin, George A.; Sood, Anil K.; Mills, Gordon B.

doi:10.1016/j.celrep.2016.04.034

Cited by 82 publications

(63 citation statements)

References 32 publications

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“…miRNAs in the nucleus have been shown to act at the promoter level affecting transcription. For example, miR-551b-3p directly upregulates STAT3 expression by binding to a complementary sequence on the STAT3 promoter, and recruiting RNA polymerase II and the TWIST1 transcription factor to activate STAT3 transcription (Chaluvally-Raghavan et al, 2016). miRNAs have also been detected in membrane-bound compartments, such as secreted vesicles (Zhang et al, 2010) and mitochondria (Das et al, 2012).…”

Section: Mirna Biogenesis and Mechanism Of Actionmentioning

confidence: 99%

microRNA Therapeutics in Cancer — An Emerging Concept

et al. 2016

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MicroRNAs (miRNAs) are an evolutionarily conserved class of small, regulatory non-coding RNAs that negatively regulate protein coding gene and other non-coding transcripts expression. miRNAs have been established as master regulators of cellular processes, and they play a vital role in tumor initiation, progression and metastasis. Further, widespread deregulation of microRNAs have been reported in several cancers, with several microRNAs playing oncogenic and tumor suppressive roles. Based on these, miRNAs have emerged as promising therapeutic tools for cancer management. In this review, we have focused on the roles of miRNAs in tumorigenesis, the miRNA-based therapeutic strategies currently being evaluated for use in cancer, and the advantages and current challenges to their use in the clinic.

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Section: Mirna Biogenesis and Mechanism Of Actionmentioning

confidence: 99%

microRNA Therapeutics in Cancer — An Emerging Concept

et al. 2016

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“…Interestingly, miR-551-3p binds to the promoter of signal transducer and activator of transcription 3 (STAT3), leading to increased expression of STAT3. Treatment of mouse models with anti-miR-551b-3p via a liposomal delivery system decreased tumor burden in vivo (69). These few pre-clinical models show promise for treatment of EOC with molecules that regulate microRNA expression.…”

Section: Microrna Molecules As Therapy For Eocmentioning

confidence: 99%

The role of MicroRNA molecules and MicroRNA-regulating machinery in the pathogenesis and progression of epithelial ovarian cancer

Wang

Ivan

Hawkins

2017

Gynecologic Oncology

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MicroRNA molecules are small, single-stranded RNA molecules that function to regulate networks of genes. They play important roles in normal female reproductive tract biology, as well as in the pathogenesis and progression of epithelial ovarian cancer. DROSHA, DICER, and Argonaute proteins are components of the microRNA-regulatory machinery and mediate microRNA production and function. This review discusses aberrant expression of microRNA molecules and microRNA-regulating machinery associated with clinical features of epithelial ovarian cancer. Understanding the regulation of microRNA molecule production and function may facilitate the development of novel diagnostic and therapeutic strategies to improve the prognosis of women with epithelial ovarian cancer. Additionally, understanding microRNA molecules and microRNA-regulatory machinery associations with clinical features may influence prevention and early detection efforts.

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“…Previous study showed that STAT3 was upregulated in CC and promoted tumor growth, invasion and metastasis 33. Furthermore, microRNA-551-3p contributed to resistance to apoptosis and increased survival and proliferation of ovarian cancer cells by activating STAT3 transcription 34. A recent study demonstrated that STAT3, an important oncogene in human cancer, was a bona fide target of BCL3 in CC cell line 21.…”

Section: Discussionmentioning

confidence: 99%

BCL3 exerts an oncogenic function by regulating STAT3 in human cervical cancer

Zhao¹,

Wang²,

Zhao³

et al. 2016

OTT

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Aberrant expression of oncogenes and/or tumor suppressors play a fundamental effect on the pathogenesis and tumorigenicity of cervical cancer (CC). B-cell CLL/lymphoma 3 (BCL3) was previously found to be a putative proto-oncogene in human cancers and regulated signal transducer and activator of transcription 3 (STAT3), a critical oncogene, in CC cell line. However, its expression status, clinical significance and biological functions in CC remain largely unclear. The expressions of BCL3 and STAT3 in CC specimens were determined by immunohistochemistry. MTT, colony formation assays and flow cytometry analysis were carried out to test proliferation and cell cycle of CC cells. Here, the levels of BCL3 were overexpressed in CC compared to adjacent cervical tissues. Furthermore, high levels of BCL3 protein were confirmed by immunoblotting in CC cells as compared with normal cervical epithelial cells. The positive expression of BCL3 was correlated with adverse prognostic features and reduced survival rate. In addition, BCL3 regulated STAT3 abundance in CC cells. STAT3 was found to be upregulated and positively correlated with BCL3 expression in CC specimens. BCL3 overexpression resulted in prominent increased proliferation and cell cycle progression in Hela cells. By contrast, inhibition of BCL3 in CaSki cells remarkably suppressed proliferative ability and cell cycle progression. In vivo studies showed that knockdown of BCL3 inhibited tumor growth of CC in mice xenograft model. Notably, we confirmed that STAT3 mediated the oncogenic roles of BCL3 in CC. In conclusion, we suggest that BCL3 serves as an oncogene in CC by modulating proliferation and cell cycle progression, and its oncogenic effect is mediated by its downstream target gene, STAT3.

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Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer

Cited by 82 publications

References 32 publications

microRNA Therapeutics in Cancer — An Emerging Concept

microRNA Therapeutics in Cancer — An Emerging Concept

The role of MicroRNA molecules and MicroRNA-regulating machinery in the pathogenesis and progression of epithelial ovarian cancer

BCL3 exerts an oncogenic function by regulating STAT3 in human cervical cancer

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