Involvement of microRNA-93, a new regulator of PTEN/Akt signaling pathway, in regulation of chemotherapeutic drug cisplatin chemosensitivity in ovarian cancer cells.
Summary of "Involvement of microRNA-93, a new regulator of PTEN/Akt signaling pathway, in regulation of chemotherapeutic drug cisplatin chemosensitivity in ovarian cancer cells."
The mechanisms underlying ovarian cancer cell resistance to cisplatin (CDDP) are not fully understood. MicroRNAs (miRNAs) play important roles in tumorigenesis and drug resistance. In this paper, we utilized microRNA array and real-time PCR to show that miR-93 is significantly up-regulated in cisplatin-resistant ovarian cancer cells. In vitro assays show that over-expression and knock-down of miR-93 regulate apoptotic activity, and thereby cisplatin chemosensitivity, in ovarian cells. Furthermore, we found that miR-93 can directly target PTEN, and participates in the regulation of the AKT signaling pathway. MiR-93 inversely correlates with PTEN expression in CDDP-resistant and sensitive human ovarian cancer tissues. These results may have implications for therapeutic strategies aiming to overcome ovarian cancer cell resistance to cisplatin.
Affiliation
Department of Gynecology Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Journal Details
This article was published in the following journal.
Name: FEBS letters
ISSN: 1873-3468
Pages: 1279-86
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22465665
- DOI: http://dx.doi.org/10.1016/j.febslet.2012.03.006
Medical and Biotech [MESH] Definitions
Smad Proteins, Inhibitory
A sub-family of smad proteins that inhibit cell signaling by RECEPTOR-REGULATED SMAD PROTEINS. They form autoinhibitory feedback loops in the TGF-BETA signaling pathway and mediate signaling cross-talk with other signaling pathways
Pten Phosphohydrolase
A lipid phosphatase that acts on phosphatidylinositol-3,4,5-trisphosphate to regulate various SIGNAL TRANSDUCTION PATHWAYS. It modulates CELL GROWTH PROCESSES; CELL MIGRATION; and APOPTOSIS. Mutations in PTEN are associated with COWDEN DISEASE and PROTEUS SYNDROME as well as NEOPLASTIC CELL TRANSFORMATION.
Janus Kinases
A family of intracellular tyrosine kinases that participate in the signaling cascade of cytokines by associating with specific CYTOKINE RECEPTORS. They act upon STAT TRANSCRIPTION FACTORS in signaling pathway referred to as the JAK/STAT pathway. The name Janus kinase refers to the fact the proteins have two phosphate-transferring domains.
Properdin
A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.
Complement Factor H
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
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