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TGFβ1I1 suppressed cell migration and invasion in colorectal cancer by inhibiting the TGF-β pathway and EMT progress
1Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. zhengxf8@126.com.
Objective:
Colorectal cancer (CRC) is the fourth leading cause of death worldwide and there is a need for more specific therapeutic targets and biomarkers for the disease. Transforming growth factor β1-induced transcript 1 (TGFΒ1I1) was reported to be downregulated in CRC tissues; however, the precise roles of TGFΒ1I1 in CRC remain unclear.
Patients And Methods:
The expression of TGFΒ1I1 in CRC cell lines and tissues was assessed by quantitative Polymerase Chain Reaction (qPCR). TGFΒ1I1 was overexpressed in SW620 and RKO cells. Cell viability was analyzed by a CCK-8 assay. The proportion of apoptotic cells was analyzed by flow cytometry. The EdU cell proliferation assay of SW620 and RKO cells after transfection was performed via flow cytometry. The migration potency of SW620 and RKO cells was analyzed using a cell migration assay. A wound healing assay was performed to assess the migration potency of SW620 and RKO cells. The invasion potency of SW620 and RKO cells after TGFΒ1I1 overexpression was analyzed. The protein levels of VEGF, TGF-β, MMP9, p-Smad2/3, N-cadherin, and E-cadherin were analyzed by Western blot.
Results:
Decreased expression of TGFΒ1I1 was found in CRC tissues and cell lines. Overexpression of TGFΒ1I1 inhibited the proliferation and induced the apoptosis of CRC cells. The overexpression of TGFΒ1I1 inhibited the migration and invasion of CRC cells. We also found that the overexpression of TGFΒ1I1 in CRC cells inhibited the TGF-β pathway and epithelial-mesenchymal transition (EMT) progress.
Conclusions:
TGFΒ1I1 suppressed cell migration and invasion in CRC by inhibiting the TGF-β pathway and EMT progress.
Insights
Transforming growth factor β1-induced transcript 1 (TGFΒ1I1) suppresses colorectal cancer (CRC) progression. Overexpressing TGFΒ1I1 inhibits CRC cell proliferation, migration, and invasion by downregulating the TGF-β pathway and epithelial-mesenchymal transition.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Colorectal cancer (CRC) is a leading cause of cancer death globally.
- There is an unmet need for novel therapeutic targets and biomarkers for CRC.
- The role of Transforming growth factor β1-induced transcript 1 (TGFΒ1I1) in CRC pathogenesis is not fully understood, despite its reported downregulation in tumor tissues.
Purpose of the Study:
- To investigate the functional role of TGFΒ1I1 in colorectal cancer.
- To determine the effects of TGFΒ1I1 on CRC cell proliferation, apoptosis, migration, and invasion.
- To elucidate the molecular mechanisms underlying TGFΒ1I1's action in CRC, focusing on the TGF-β pathway and epithelial-mesenchymal transition (EMT).
Main Methods:
- Quantitative Polymerase Chain Reaction (qPCR) to assess TGFΒ1I1 expression in CRC cell lines and tissues.
- Overexpression of TGFΒ1I1 in SW620 and RKO CRC cell lines.
- Cell viability (CCK-8 assay), apoptosis (flow cytometry), proliferation (EdU assay), migration (cell migration and wound healing assays), and invasion assays.
- Western blot analysis to evaluate protein levels of key signaling molecules (VEGF, TGF-β, MMP9, p-Smad2/3, N-cadherin, E-cadherin).
Main Results:
- TGFΒ1I1 expression was significantly decreased in CRC tissues and cell lines.
- Overexpression of TGFΒ1I1 markedly inhibited CRC cell proliferation and induced apoptosis.
- TGFΒ1I1 overexpression suppressed CRC cell migration and invasion.
- Inhibition of the TGF-β pathway and EMT progress was observed upon TGFΒ1I1 overexpression in CRC cells.
Conclusions:
- TGFΒ1I1 functions as a tumor suppressor in colorectal cancer.
- TGFΒ1I1 inhibits CRC cell migration and invasion by suppressing the TGF-β signaling pathway and EMT.
- TGFΒ1I1 represents a potential therapeutic target for colorectal cancer treatment.
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