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Shu Gong

Bio: Shu Gong is an academic researcher from Sichuan University. The author has contributed to research in topics: Cancer cell & Cancer. The author has an hindex of 5, co-authored 7 publications receiving 84 citations.

Papers
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Journal ArticleDOI
Shu Gong1, Dongsheng Xu1, Jialin Zhu1, Fangdong Zou1, Rui Peng1 
TL;DR: Cobimetinib appeared to enhance the efficacy of 5-fluorouracil (5-FU) by decreasing TYMS expression, high expression of which is responsible for 5-FU resistance in colorectal cancer.
Abstract: Background/aims Mutations in the Ras/Raf/MEK/ERK pathway are detected in 50% of colorectal cancer cases and play a crucial role in cancer development and progression. Cobimetinib is a MEK inhibitor approved for the treatment of advanced melanoma and inhibits the cell viability of other types of cancer cells. Methods HCT116 colorectal cancer cells were treated with cobimetinib, and MTT assay, colony formation assay, and flow cytometry were used to evaluate cell viability, cell cycle, and apoptosis, respectively. The expression of genes associated with the cell cycle and apoptosis were evaluated by quantitative real-time PCR and western blotting. To explore use of cobimetinib in colorectal cancer treatment and further understand its mechanisms, RNA-seq technology was used to identify differentially expressed genes (DEGs) between cobimetinib-treated and untreated HCT116 cells. Furthermore, we compared these DEGs with Gene Expression Omnibus data from colorectal cancer tissues and normal colonic epithelial tissues. Results We found that cobimetinib not only inhibited cell proliferation but also induced G1 phase arrest and apoptosis in HCT116 colorectal cancer cells, suggesting that cobimetinib may useful in colorectal cancer therapy. After cobimetinib treatment, 3,495 DEGs were obtained, including 2,089 upregulated genes and 1,406 downregulated genes, and most of these DEGs were enriched in the cell cycle, DNA replication, and DNA damage repair pathways. Our results revealed that some genes with high expression in colorectal cancer tissues were downregulated by cobimetinib in HCT116 cells, including CCND1, E2F1, CDC25C, CCNE2, MYC, and PCNA. These genes have vital roles in DNA replication and the cell cycle. Furthermore, genes with low expression in colorectal cancer tissues were upregulated by cobimetinib, including PRKCA, PI3K, RTK, and PKC. Based on our results, the PKC and PI3K pathways were activated after cobimetinib treatment, and inhibition of these two pathways can increase the cytotoxicity of cobimetinib in HCT116 cells. Notably, cobimetinib appeared to enhance the efficacy of 5-fluorouracil (5-FU) by decreasing TYMS expression, high expression of which is responsible for 5-FU resistance in colorectal cancer. Conclusions Our results suggest the potential use of cobimetinib in colorectal cancer therapy.

28 citations

Journal ArticleDOI
Ziqi Zhang1, Tong Sun1, Yuxi Chen1, Shu Gong1, Xiye Sun, Fangdong Zou1, Rui Peng1 
TL;DR: The findings suggested that CCL25/CCR9 signal may provide cancer cells with chemotactic abilities through influencing several EMT markers, and resulted in different promotion of migration and invasion in different cell lines.
Abstract: Cancer is one of the most lethal diseases worldwide, and metastasis is the most common cause of patients' deaths. Identification and inhibition of markers involved in metastasis process in cancer cells are promising works to block metastasis and improve prognoses of patients. Chemokines are a superfamily of small, chemotactic cytokines, whose functions are based on interaction with corresponding receptors. It has been found that one of the functions of chemokines is to regulate migration and invasion abilities of lymphocytes, as well as cancer cells. Chemokine receptor 9 (CCR9) regulates trafficking of lymphocytes and cancer cell lines when interacting with its exclusive ligand chemokine 25 (CCL25). However, the mechanisms of CCL25/CCR9 signal that regulates metastasis of cancer cells are not completely known yet. In this study, we stimulated or inhibited CCL25/CCR9 signal in breast cancer cell line (MDA-MB-231) and hepatocellular cancer cell lines (HepG2 and HUH7), and found that CCL25/CCR9 signal resulted in different promotion of migration and invasion in different cell lines. These phenomena could be explained by selective regulation of several markers of epithelial-mesenchymal transition (EMT). Our findings suggested that CCL25/CCR9 signal may provide cancer cells with chemotactic abilities through influencing several EMT markers.

27 citations

Journal ArticleDOI
25 May 2013-Gene
TL;DR: The results suggested that Tibetan argali and Gansu argali may belong to the same subspecies (O. hodgsoni) of O. ammon, rather than two different subspecies.

22 citations

Journal ArticleDOI
TL;DR: It is demonstrated that (-)-curine can inhibit viability of hepatocellular carcinoma cells in regardless of p53 status, and shed light on new therapy methods for HCC.

10 citations

Journal ArticleDOI
Liyuan Wu1, Si Li, Rui Peng, Shu Gong, Liu Xu, Fangdong Zou 
TL;DR: MiR-21 can mediate the drug resistance to 5-FU by inhibiting its target PDCD4, which can regulate the expression of ABCC5 and CD44 genes.
Abstract: OBJECTIVE To explore downstream regulatory pathway of microRNA-21 (miR-21) in colon cancer cells (RKO) through detecting miR-21 and its target PDCD4, and the influence of miR-21 regulation on the sensitivity of RKO cells to 5-fluorouracil (5-FU). METHODS 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the effect of 5-FU on the viability of RKO cells with knockout of miR-21 or high expression of PDCD4. Real-time was used to determine the expression of PDCD4, ABCC5 and CD44 in RKO cell after knockout of miR-21. RESULTS MTT assay reveals that the IC50 of 5-FU in RKO-WT cells (52.82 ± 0.06 umol/L) was about 67% higher than in miR-21 knockout cells (32.23 ± 0.05 umol/L) (P < 0.05), and the apoptosis ratio elevated after knockout of miR-21. High expression of PDCD4, a target gene of miR-21, can negatively regulate the expression of ABC transporter ABCC5 and the stem cell marker CD44. CONCLUSION MiR-21 can mediate the drug resistance to 5-FU by inhibiting its target PDCD4, which can regulate the expression of ABCC5 and CD44 genes.

8 citations


Cited by
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Journal ArticleDOI
TL;DR: Functional and mechanistic study revealed that CXCL13 promoted the proliferation and migration of ccRCC cells by binding to CXCR5 and activated PI3K/AKT/mTOR signaling pathway, and suggested that CxCL13/CX CR5 axis played a significant role in ccR CC and might be a therapeutic target and prognostic biomarker.
Abstract: The chemokine ligands and their receptors play critical roles in cancer progression and patients outcomes. We found that CXCL13 was significantly upregulated in ccRCC tissues compared with normal tissues in both The Cancer Genome Atlas (TCGA) cohort and a validated cohort of 90 pairs ccRCC tissues. Statistical analysis showed that high CXCL13 expression related to advanced disease stage and poor prognosis in ccRCC. We also revealed that serum CXCL13 levels in ccRCC patients (n = 50) were significantly higher than in healthy controls (n = 40). Receiver operating characteristic (ROC) curve revealed that tissue and serum CXCL13 expression might be a diagnostic biomarker for ccRCC with an area under curve (AUC) of 0.809 and 0.704, respectively. CXCL13 was significantly associated with its receptor, CXCR5, in ccRCC tissues, and ccRCC patients in high CXCL13 high CXCR5 expression group have a worst prognosis. Functional and mechanistic study revealed that CXCL13 promoted the proliferation and migration of ccRCC cells by binding to CXCR5 and activated PI3K/AKT/mTOR signaling pathway. These results suggested that CXCL13/CXCR5 axis played a significant role in ccRCC and might be a therapeutic target and prognostic biomarker.

70 citations

Journal ArticleDOI
TL;DR: The current knowledge about the potential roles of miRNAs in 5‐FU resistance, with particular emphasis on molecular mechanism involved, is summarized.
Abstract: Colorectal cancer (CRC) is one of the most common cancers globally. Despite recent advances in therapeutic approaches, this cancer continues to have a poor prognosis, particularly when diagnosed late. 5-Fluorouracil (5-FU) has been commonly prescribed for patients with CRC, but resistance to 5-FU is one of the main reasons for failure in the treatment of this condition. Recently, microRNAs (miRNAs) have been established as a means of modifying the signaling pathways involved in initiation and progression of CRC and their role as oncogene or tumor suppressor have been investigated in various studies. Moreover, miRNAs through various mechanisms play an important role in inducing tumor resistance or sensitivity to anticancer drugs. Detecting and targeting these mechanisms may be a new therapeutic approach. This review summarizes the current knowledge about the potential roles of miRNAs in 5-FU resistance, with particular emphasis on molecular mechanism involved.

54 citations

Journal Article
TL;DR: The first review that aims to consider and dissect all of the elucidated complex behaviors of E2F1 in colon cancer is provided, which provides an analysis and conclusion regarding the current understanding of E 2F1In colon cancer in order to facilitate the direction of future research.
Abstract: E2F transcription factor 1 (E2F1) is a member of the E2F family of transcription factors. E2F1 binds to DNA with dimerization partner (DP) proteins through an E2 recognition site. The dissociation of E2F1 from retinoblastoma (Rb) protein recovers its transcriptional activity, which drives the cell cycle from the G1 to S phase. E2F1 has been shown to be involved in cellular proliferation, differentiation, and apoptosis in colon cancer. It was recently found that E2F1 also participates in the metastasis and chemoresistance of colon cancer. There are abundant experimental data regarding the actions of E2F1, which can be grouped as either pro-tumorigenic or pro-apoptotic. Despite a growing interest and plentiful data, there is currently no review that focuses on the role of E2F1 in colon cancer. Research on E2F1 and colon cancer has been scattered over various genes and microRNAs (miRNAs) that affect E2F1 expression. Here, we provide the first review that aims to consider and dissect all of the elucidated complex behaviors of E2F1 in colon cancer. This review also provides an analysis and conclusion regarding the current understanding of E2F1 in colon cancer in order to facilitate the direction of future research.

51 citations

Journal ArticleDOI
TL;DR: Increased level of METTL3 may maintain the tumorigenicity of colon cancer cells by suppressing SOCS2, and m6A-RNA immunoprecipitation-qPCR revealed that SOCS 2 mRNA was targeted byMETTL3 for m6a modification.
Abstract: N6‑methyladenosine (m6A) RNA modification maintained by N6‑methyltransferases and demethylases is involved in multiple biological functions Methyltransferase like 3 (METTL3) is a major N6‑methyltransferase However, the role of METTL3 and its installed m6A modification in colorectal tumorigenesis remains to be fully elucidated METTL3 is highly expressed as indicated in colorectal cancer samples in the TCGA and Oncomine databases, implying its potential role in colon tumorigenesis SW480 cell line with stable METTL3 knockout (METTL3‑KO) was generated using CRISPR/Cas9 and were confirmed by the loss of METTL3 expression and suppression of m6A modification The proliferation of METTL3‑KO cells was significantly inhibited compared with that of control cells METTL3‑KO decreased the decay rate of suppressor of cytokine signaling 2 (SOCS2) RNA, resulting in elevated SOCS2 protein expression m6A‑RNA immunoprecipitation‑qPCR (MeRIP‑qPCR) revealed that SOCS2 mRNA was targeted by METTL3 for m6A modification Similar to METTL3‑KO SW480 cells, SW480 cells treated with 3‑deazaadenosine, an RNA methylation inhibitor, exhibited elevated SOCS2 protein expression Increased levels of SOCS2 in METTL3‑KO SW480 cells were associated with decreased expression of leucine‑rich repeat‑containing G protein‑coupled receptor 5 (LGR5), contributing to the inhibition of cell proliferation The underlying associations among METTL3, SOCS2, and LGR5 were further confirmed in SW480 cells transfected with si‑METTL3 and in tumor samples from patients with colorectal cancer Taken together, our data demonstrate that an increased level of METTL3 may maintain the tumorigenicity of colon cancer cells by suppressing SOCS2

51 citations

Book ChapterDOI
TL;DR: Better understanding of molecular footprint of cancer cells, as well as crosstalk between cancer cells and host immune system is needed to develop patient specific treatment and management of breast cancer.
Abstract: Breast cancer touches women's life worldwide. Expected outcome is not achieved due to molecular heterogeneity and complex biology despite substantial advancement in diagnosis, prevention and treatment of breast cancer. Patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (Her2) positive tumors receive hormone ablation and Her2 directed therapy. While patients diagnosed with triple-negative breast cancer receive chemotherapy in both the early and advanced stages. However, chemotherapeutic efficacies are not the same in every patient, which has fostered a major effort to identify new targets to treat breast cancer. Positive therapeutic outcome after immune checkpoint inhibitors emphasizes the significance of the host immune system in breast cancer. Cancer develops in immune competent host wherein cytokines, while shaping the immune system, also serve as growth signals for cancer cells. The dynamics of cross talk between immune system and cancer cells mediated by cytokines and chemokines changes during cancer initiation, progression, and therapeutic interventions. Hence, better understanding of molecular footprint of cancer cells, as well as crosstalk between cancer cells and host immune system is needed to develop patient specific treatment and management of breast cancer.

48 citations