Cancer-associated fibroblasts promote metastatic potential of colorectal cancer cell by provoking long noncoding RNA UCA1

Publish Year: 1397
نوع سند: مقاله کنفرانسی
زبان: English
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CIGS15_011

تاریخ نمایه سازی: 13 بهمن 1398

Abstract:

Cancer-associated fibroblasts (CAFs) play an important role in malignant behavior in colorectal cancer (CRC). However, little is known about how they impact tumor metastasis and underlying mechanisms remain largely elusive. Dysregulation of long noncoding UCA1 is also associated with metastasis in various cancers including CRC. In this study, the effects of conditioned medium from CRC CAFs (CAF-CM) on EMT, invasion, and migration of treated CRC cell was evaluated in vitro and expression of UCA1/mTOR/miR-143/KRAS signaling pathway determined by qRT-PCR or western blot. Our study indicated that CAFs dramatically stimulated invasion and migration of CRC cell. Furthermore, CAFs induced the EMT phenotype in CRC cell, with an associated change in the expression of EMT markers including vimentin, E-cadherin, N-cadherin and incited metastasis-related genes (MMPs). The following mechanism investigation revealed that CAFs induced overexpression of UCA1, which leads to upregulation of mTOR. Overexpression of UCA1/mTOR axis suppressed miR-143 while KRAS was significantly upregulated in mRNA and protein level compared with control group. Moreover, UCA1 silencing in treated CRC cell suggested that overexpression of UCA1, which was induced by CAFs, regulates the expression of downstream key effectors. Taken together, these findings provide a better discernment of intercellular communication whereby CAFs incite the UCA1/mTOR axis to direct CRC cell invasive manner. These study support the hypothesis that CAFs may be a prominent therapeutic target of stroma-based therapy in CRC treatment, besides the critical role of cooperation between UCA1 and mTOR in cancer metastasis.

Authors

Babak Jahangiri

Department of Genetics, Faculty of Natural Science, University of Tabriz, Tabriz, Iran,Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

Mohammad Khalaj-kondori

Department of Genetics, Faculty of Natural Science, University of Tabriz, Tabriz, Iran

Elahe Asadollahi

Department of Biochemistry, Protein Research Center, University of Shahid Behshti, G.C, Tehran, Iran

Majid Sadeghizadeh

Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran