Shen H, Wang GC, Li X, Ge X, Wang M, Shi ZM, Bhardwaj V, Wang ZX, Zinner RG, Peiper SC, Aplin AE, Jiang BH, He J*. S6K1 blockade overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer. Oncogene, 2020, October 9.

In this study, we identified S6K1/MDM2 signaling axis as a novel bypass mechanism for the development of EGFR-TKI resistance. The observation of S6K1 as a candidate mechanism for resistance to EGFR TKI therapy was investigated by interrogation of public databases and a clinical cohort to establish S6K1 expression as a prognostic/predictive biomarker. The role of S6K1 in TKI resistance was determined in in vitro gain-and-loss of function studies and confirmed in subcutaneous and orthotopic mouse lung cancer models. Blockade of S6K1 by a specific inhibitor PF-4708671 synergistically enhanced the efficacy of TKI without showing toxicity. The mechanistic study showed the inhibition of EGFR caused nuclear translocation of S6K1 for binding with MDM2 in resistant cells. MDM2 is a downstream effector of S6K1-mediated TKI resistance. 

He J, Yu JJ, Xu Q, Wang L, Zheng J, Liu LZ, Jiang BH. Downregulation of ATG14 by EGR1-MIR152 sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cytoprotective autophagy. Autophagy, 2015, 11: 373-84. PMID: 25650716; PMCID: PMC4502709.

This paper showed that miR-152 as a new autophagy-regulating miRNA that is critical in cisplatin-resistance. We identified that ATG14 is a functional target of MIR152 in regulating autophagy inhibition. Furthermore, we found that EGR1 (early growth response 1) regulated the MIR152 gene at the transcriptional level. More importantly, these findings were relevant to clinical cases.

He J, Wang M, Jiang Y, Chen Q, Xu S, Xu Q, Liu LZ, Jiang BH. Chronic arsenic exposure and angiogenesis in human bronchial epithelial cells via ROS/miR-199a-5p/HIF-1α/COX-2 Pathway. Environmental Health Perspectives, 2014, 122: 255-61

This paper demonstrated the critical roles of miR-199a-5p and its downstream targets HIF-1/COX-2 in arsenic-induced tumor growth and angiogenesis.

He J, Xu Q, Jing Y, Agani F, Carpenter R, Qian X, Li Q, Wang XR, Peiper SS, Lu Z, Liu LZ, Jiang BH. Reactive oxygen species regulate ERBB2 and ERBB3 expression via miR-199a/125b and DNA methylation. EMBO Rep., 2012, 13(12): 1116-1122.

Overexpression of ERBB2 or ERBB3 is associated with cancer development and poor prognosis. In this study, we show that reactive oxygen species (ROS) induce both ERBB2 and ERBB3 expression through miR-199a and miR-125b. We also identify that ROS inhibit miR-199a and miR-125b expression through DNA methylation.

Complete List of Published Work in My Bibliography:

https://www.ncbi.nlm.nih.gov/myncbi/jun.he.3/bibliography/public/