CREB1-driven expression of miR-320a promotes mitophagy by down-regulating VDAC1 expression during serum starvation in cervical cancer cells
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Qin-qin Li1,*, Le Zhang1,*, Hai-ying Wan1,*, Min Liu1, Xin Li1, Hua Tang1
1Tianjin Life Science Research Center and School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
*These authors have contributed equally to this work
Hua Tang, e-mail: [email protected]
Keywords: CREB1, miR-320a, mitophagy, serum starvation, VDAC1
Received: April 26, 2015 Accepted: October 02, 2015 Published: October 14, 2015
The altered expression of miRNAs in response to stresses contributes to cancer pathogenesis. However, little is known regarding the mechanism by which cellular stresses drive alterations in miRNA expression. Here, we found that serum starvation enhanced mitophagy by downregulating the mitophagy-associated protein voltage-dependent anion channel 1 (VDAC1) and by inducing the expression of miR-320a and the transcription factor cAMP responsive element binding protein 1(CREB1). Furthermore, we cloned the promoter of miR-320a and identified the core promoter of miR-320a in the upstream −16 to −130 region of pre-miR-320a. Moreover, CREB1 was found to bind to the promoter of miR-320a to activate its expression and to induce mitophagy during serum starvation. Collectively, our results reveal a new mechanism underlying serum starvation-induced mitophagy in which serum starvation induces CREB1 expression, in turn activating miR-320a expression, which then down-regulates VDAC1 expression to facilitate mitophagy. These findings may provide new insights into cancer cell survival in response to environmental stresses.
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