Cancer-associated fibroblasts-derived extracellular vesicles carrying lncRNA SNHG3 facilitate colorectal cancer cell proliferation via the miR-34b-5p/HuR/HOXC6 axis

Jiangning Zhao; Huanrong Lin; Kunsong Huang; Shen Li

doi:10.1038/s41420-022-01116-z

Cancer-associated fibroblasts-derived extracellular vesicles carrying lncRNA SNHG3 facilitate colorectal cancer cell proliferation via the miR-34b-5p/HuR/HOXC6 axis

Cell Death Discov. 2022 Aug 3;8(1):346. doi: 10.1038/s41420-022-01116-z.

Authors

Jiangning Zhao^#¹, Huanrong Lin^#², Kunsong Huang³, Shen Li²

Affiliations

¹ Gastrointestinal Peritoneal Cancer Surgery, The Fourth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, Guangdong, China. zhaojiangning0828@163.com.
² Gastrointestinal Peritoneal Cancer Surgery, The Fourth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, Guangdong, China.
³ Department of General Surgery, Guangzhou Overseas Chinese Hospital, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, China.

^# Contributed equally.

Abstract

Cancer-associated fibroblasts (CAFs)-derived extracellular vesicles (EVs) can mediate tumorigenesis. Long noncoding RNA (LncRNA) SNHG3 is implicated in colorectal cancer (CRC) progression. The current study sought to clarify the role of CAFs-EVs carrying SNHG3 in CRC cell proliferation. Firstly, CAFs and normal fibroblasts (NFs) were cultured and identified, followed by isolation and characterization of CAFs-EVs and NFs-EVs. CRC cells were cultured with CAFs-EVs or CAFs-EVs overexpressing SNHG3. The effects of SNHG3 on CRC cell proliferation was evaluated using CCK-8, colony formation, and EdU staining assays. The binding relationships among SNHG3, miR-34b-5p, and HuR were validated, in addition to analyzing the binding between HuR and HOXC6. Lastly, xenograft tumor model was established to verify the role of CAFs-EVs carrying SNHG3 in vivo. SNHG3 was highly expressed in CRC cells and CAFs-EVs, whereas CAFs-EVs facilitated CRC cell proliferation. Mechanically, CAFs-EVs carried SNHG3 into CRC cells to upregulate HuR expression by competitively binding to miR-34b-5p, promote the binding of HuR and HOXC6, and enhance HOXC6 transcription. miR-34b-5p over-expression or HOXC6 silencing annulled the effect of CAFs-EVs. SNHG3 carried by CAFs-EVs facilitated CRC proliferation via the miR-34b-5p/HuR/HOXC6 axis in vivo. Collectively, our findings indicated that CAFs-EVs carried SNHG3 into CRC cells to upregulate HuR expression by sponging miR-34b-5p and finally enhance HOXC6 transcription, thereby facilitating CRC cell proliferation.