He Research

Li X, Wang S, Mu W, Barry J, Han A, Carpenter RL, Jiang BH, Peiper SC, Mahoney MG, Aplin AE, Ren H, He J*. Reactive oxygen species reprogram macrophages to suppress antitumor immune response through the exosomal miR-155-5p/PD-L1 pathway. J Exp Clin Cancer Res. 2022 Jan 27; 41(1):41.

Our findings demonstrate a novel mechanism, ROS-induced down-regulation of miR-155-5p, by which tumors modulate the microenvironment in favor of tumor progression. Understanding the negative impact of ROS on the tumor immune response will improve current therapeutic strategies. Targeting miR-155-5p can be an alternative approach to prevent formation of an immunosuppressive TME through downregulation of PD-L1 and other immunosuppressive factors.

Ge X*, He J*, Wang L, Zhao L, Wang Y, Wu G, Liu W, Shu Y, Gong W, Ma XL, Wang Y, Jiang BH, Liu LZ. Epigenetic alterations of CXCL5 in Cr (VI)-induced carcinogenesis. Sci Total Environ. 2022 Sep 10; 838:155713. *co-first author

Through a population-based cross-sectional study, we identified that the expression levels of CXCL5 were highly upregulated in PBMCs samples from workers with occupational exposure to Cr (VI) compared with those in control subjects, and the CXCL5 levels were positively correlated with total Cr concentrations in subjects' toenails. Mechanistic studies showed that elevated CXCL5 expression levels were regulated by Cr (VI)-induced histone modifications and DNA hypomethylation, and that the c-Myc/p300 complex was a key upstream regulator of histone H3 acetylation. CXCL5 overexpression promoted Cr(VI)-induced EMT by upregulating zinc finger E-box binding homeobox 1 (ZEB1) to promote tumor development.

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. 

4. 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.

The cyto-protective functions of autophagy in cancer cells have been suggested as a potential mechanism for chemoresistance. 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, EGR1 (early growth response 1) regulates the MIR152 gene at the transcriptional level. More importantly, these findings were relevant to clinical cases. Both EGR1 and MIR152 expression levels were significantly lower in ovarian cancer tissues with high levels of ERCC1 (excision repair cross-complementation group 1), a marker for cisplatin-resistance. Activation of EGR1 and MIR152 may serve as an useful therapeutic strategy to overcome cisplatin-resistance by preventing cyto-protective autophagy in ovarian cancer.

Complete list of published qork in my bibliography: