MicroRNA-204 modulates colorectal cancer cell sensitivity in response to 5-fluorouracil-based treatment by targeting high mobility group protein A2

Wu, Haijian; Shen, Lin; Shen, Liangfang

doi:10.1242/bio.015008

Cited by 58 publications

(48 citation statements)

References 40 publications

(48 reference statements)

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“…The results showed that 5‐FU suppressed the cell viability in a concentration‐dependent manner; after the PCAT6 knockdown, the IC50 values of HCT116 and SW480 cells were reduced from 15.42 and 14.74 to 7.63 and 7.50, respectively (Figure D,E). In our previous study, the HMGA2/PI3K signaling pathway is involved in CRC cell proliferation; herein, we investigated whether PCAT6 could regulate HMGA2. In HCT116 and SW480 cells, PCAT6 knockdown significantly reduced the protein levels of HMGA2 (Figure F,G).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, lncRNA has been reported to target miRNAs, thus interacting with miRNAs and participating in either normal physiological processes or pathogenic processes . We revealed that miR‐204/HMGA2 axis modulates CRC cell sensitivity to 5‐FU; herein, we investigated whether PCAT6 could interact with miR‐204, thereby affecting CRC chemoresistance to 5‐FU. The expression of miR‐204 was determined in si‐PCAT6 transfected HCT116 and SW480 cells by real‐time PCR assays.…”

Section: Resultsmentioning

confidence: 99%

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Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signaling

Zou

et al. 2019

Cancer Medicine

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Colorectal cancer (CRC) is still the third most common cancer in the world with a limited prognosis due to the chemoresistance of CRC cells to 5‐fluorouracil (5‐FU)‐based chemotherapy. In our previous study, we revealed that miR‐204 overexpression could sensitize CRC cell to 5‐FU treatment through targeting HMGA2/PI3K signaling pathway; however, miR‐204 expression in CRC tissues is abnormally downregulated. Long non‐coding RNAs (lncRNAs) dysregulation has been reported in human diseases, including cancer. Also, lncRNA can regulate cancer cell proliferation, invasion, migration, as well as chemoresistance. LncRNA prostate cancer‐associated transcript 6 (PCAT6) acts as an oncogene in many cancers; herein, PCAT6 expression was abnormally upregulated in CRC tissues and cell lines, suggesting its potential role in CRC. Further, we assessed the specific function and mechanism of PCAT6 in CRC. Furthermore, we revealed that PCAT6 knockdown attenuated CRC chemoresistance to 5‐FU through miR‐204/HMGA2/PI3K; miR‐204 inhibition could partially reverse the effect of PCAT6 knockdown. Taken together, we demonstrate that the abnormal PCAT6 overexpression inhibits miR‐204 expression in CRC, thereby promoting HMGA2/PI3K signaling activity, ultimately enhancing the chemoresistance of CRC cells to 5‐FU; PCAT6 represents a promising target for dealing with CRC chemoresistance.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signaling

Zou

et al. 2019

Cancer Medicine

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“…The miR-204/HMGA2 axis modulated the resistance of tumor cells to 5-FU in HCT-116 and SW480 colon cancer cells via activation of the PI3K/AKT pathway. These results demonstrate that the miR-204/HMGA2 axis could play a vital role in the 5-FU resistance of colon cancer cells [57].…”

Section: Introductionmentioning

confidence: 60%

MicroRNAs as Regulators, Biomarkers and Therapeutic Targets in the Drug Resistance of Colorectal Cancer

Xie

Huang

Wang

et al. 2016

Cell Physiol Biochem

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Chemotherapy and targeted therapy are the main options for andvanced colorectal cancer (CRC). However, resistance to these therapies is a major challenge in the clinic. Understanding molecular mechanisms and developing effective strategies against the drug resistance are highly desired. Increasing evidence has revealed that microRNAs (miRNAs) are closely linked to drug resistance in CRC. The explosion of knowledge in this field has brought forward new predictive and therapeutic opportunities. In this review, we systemically summarize the roles of miRNAs as regulators, tissue or circulating biomarkers, and therapeutics in the CRC resistance to 5-fluorouracil (5-FU), oxaliplatin and anti-EGFR therapy. We also discuss the potential unsettled issues and future directions concerning these processes.

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“…Moreover, downregulated miRNA-204 is frequently coupled with tumor suppressive activity in multiple tumors [10][11][12][13]. In parallel with this evidence, we analyzed the expressions of miR-204 in human gastric tumors, and compared with their adjacent normal tissues.…”

Section: Mir-204 Is Downregulated In Gc and Suppresses Proliferation mentioning

confidence: 91%

“…Increasing evidences have indicated that miRNAs play a major role in various types of cancers, including cancer cell, proliferation, differentiation, apoptosis, chemo-sensitivity, metastasis, tumorigenesis, and cellular metabolism [8,9]. It has been reported that miR-204 was downregulated in multiple cancers [10][11][12][13]. However, the mechanisms of miR-204 in 5-FU sensitivity in GC are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Sensitization of Gastric Cancer Cells to 5-FU by MicroRNA-204 Through Targeting the TGFBR2-Mediated Epithelial to Mesenchymal Transition

Pan

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Gastric cancer (GC) is the most common gastrointestinal malignancy, causing cancer-related deaths in East Asia. MicroRNAs (miRNAs) are small non-coding RNAs aberrantly expressed in human tumors. In this study, we aim to investigate the roles of miR-204 in the epithelial to mesenchymal transition (EMT)-associated chemosensitivity. Methods: The expression of miR-204 was detected in clinical tumor samples and GC cell lines by real time PCR. Tumor cell’s growth, invasion, and migration were measured by MTT assay, wound healing assay, and transwell invasion assay, respectively. Western blot method was used to detect the protein levels of indicated genes. Luciferase reporter assay was performed to validate the target gene of miR-204. The in vivo role of miR-204 was measured using a xenograft mouse model of GC. Results: By comparing the expressions of miR-204 in human gastric tumors and their adjacent normal tissues, it was disclosed that miR-204 was significantly downregulated in gastric tumors. Moreover, miR-204 was downregulated in multiple GC cell lines compared with normal gastric epithelial cells. Overexpression of miR-204 suppressed GC cells’ proliferation, invasion, and migration. It is noteworthy that 5-FU treatments induced miR-204 expression and suppressed TGF-β pathway. By establishment of 5-FU resistant GC cell line, it was revealed that miR-204 was significantly downregulated in 5-FU resistant GC cells, representing mesenchymal features with downregulation of epithelial marker, while mesenchymal markers were upregulated. We identified TGFBR2 as a direct target of miR-204 by Western blot method and luciferase assay in GC cells and tumor samples as well. In addition, overexpression of miR-204 sensitized GC cells to 5-FU in vitro. Xenograft experiments demonstrated that the combination of miR-204 and 5-FU efficiently inhibited tumor growth and improved survival rate of mice as well. Eventually, we illustrated the restoration of TGFBR2 in miR-204 overexpression GC cells, which recovered resistance to 5-FU treatments compared with miR-204 overexpression GC cells. Conclusion: This study describes a miRNA-based therapeutic strategy against 5-FU resistance in GC, contributing to the development of anti-chemoresistance therapeutic agents.

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MicroRNA-204 modulates colorectal cancer cell sensitivity in response to 5-fluorouracil-based treatment by targeting high mobility group protein A2

Cited by 58 publications

References 40 publications

Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signaling

Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signaling

MicroRNAs as Regulators, Biomarkers and Therapeutic Targets in the Drug Resistance of Colorectal Cancer

Sensitization of Gastric Cancer Cells to 5-FU by MicroRNA-204 Through Targeting the TGFBR2-Mediated Epithelial to Mesenchymal Transition

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