Recently, Professor Li Gang’s team of the Department of Neurosurgery of Qilu Hospital of Shandong University has made a series of research achievements in the field of molecular regulation of glioma. Three academic papers have been published in the first area international journals of Chinese Academy of Sciences, including
JECCR and
Oncogene.
Professor Li Gang's team revealed a new mechanism of ARPC1B promoting radiotherapy tolerance in glioblastoma. Although glioma stem cells account for a small proportion in gliomas, they have low differentiation and high carcinogenic ability, and are related to radiotherapy and chemotherapy resistance. Glioma stem cells are mainly divided into two subtypes: PN and MES, in which MES type has higher invasiveness and chemotherapy resistance. The team confirmed for the first time that ARPC1B is highly expressed in MES glioma stem cells, and that ARPC1B can maintain the stability of IFI16 and HuR respectively by inhibiting TRIM21-mediated ubiquitin degradation, and then promote the PMT of glioma stem cells through the activation of NF-κB pathway induced by IFI16 and the activation of STAT3 pathway induced by HuR, respectively, so that glioblastoma can obtain stronger radiotherapy tolerance. High-throughput screening further found that AZD6738, a targeted drug, was related to the expression of ARPC1B, and its combination with radiotherapy could play a stronger anti-tumor effect, which provided a new intervention strategy of combined radiotherapy and chemotherapy for glioblastoma. The research results were published in the prestigious international magazine
Journal of Experimental & Clinical Cancer Research (Chinese Academy of Sciences(CAS) Journal ranking Q1, latest IF：12.658) in November, 2022 under the title "ARPC1B Promotes Mesenchymal Phenotype Maintenance and Radiotherapy Resistance by Blocking TRIM21-Mediated Degradation of IFI16 and HuR in Glioma Stem Cells". Gao Zijie, Xu Jianye and Fan Yang, postgraduates of neurosurgery in Qilu Hospital of Shandong University, are co-first authors of this article, Professor Li Gang and Associate Researcher Guo Xing are co-corresponding authors, and Qilu Hospital of Shandong University is the first and the communication author’s affiliation.
Professor Li Gang's team discovered the mechanism of hypoxia-induced circular RNA circADAMTS6 promoting the malignant progression of glioblastoma. The team described the expression profile of circular RNA in glioblastoma under hypoxia for the first time, and screened out the circular RNA-circADAMTS6 which was most significantly up-regulated in glioblastoma under hypoxia, which confirmed that hypoxia can not only mediate the transcriptional activation of ADAMTS6 pre-mRNA through JUN protein, but also regulate the cycling process of circADAMTS6 mediated by TDP43 protein, thus promoting the high expression of circADAMTS6. The research results were published in
Oncogene (CAS Journal ranking Q1, latest IF：8.756) entitled "Hypoxia-induced circADAMTS6 in a TDP43-dependent manner accelerates glioblastoma progression via ANXA2/ NF-κB pathway " in November 2022. Zhao Shulin, a doctoral student majored in neurosurgery in Qilu Hospital of Shandong University, is the first author of this article, Professor Li Gang and Associate Professor Xue Hao are the co-authors, and Qilu Hospital of Shandong University is the first and the corresponding author’s affiliation.
Professor Li Gang's team further clarified the new dual mechanism of glioma exocrine promoting tumor. In the previous study, the research group classified the sequenced miRNA (Cell Death Dis. 2022 May 2: 13 (5): 2022), further screened the exocrine type representative miR-3591-3p, which confirmed that it can inhibit the proliferation and induce apoptosis of glioma by targeting MAPK1 protein and then affecting the MAPK signal pathway. Further studies have found that glioma cells can also excrete tumor suppressor miR-3591-3p from tumor cells through exocrine bodies to promote tumor-associated macrophages in immune microenvironment to produce stronger immunosuppressive ability and jointly promote the malignant progression of tumors. The research results were published in
Oncogene (CAS Journal ranking Q1, latest IF：8.756) in September 2022 under the title "Tumor-derived exosomes deliver the tumor suppressor miR-3591-3p to induce M2 macrophage polarization and promote glioma progression". Li Ming, a doctoral student majored in neurosurgery in Qilu Hospital of Shandong University, is the first author of, Professor Li Gang and Associate Professor Xue Hao are co-authors, and Qilu Hospital of Shandong University is the first and the corresponding author’s affliation.
The above researches have been supported by the National Natural Science Foundation of China, Mount Tai Scholars climbing Program and other projects. At the same time, they are also supported by platforms including the Provincial Key Laboratory of Brain Function Reconstruction in Shandong Province, the Institute of Brain and Brain-like Science of SDU, and the National Health and Medical Data Science Institute.
