microRNA-577 suppresses tumor growth and enhances chemosensitivity in colorectal cancer.
In this work, we aimed to determine the expression and biological functions of microRNA (miR)-577 in colorectal cancer (CRC). The results showed that miR-577 was downregulated in CRC specimens and cell lines. Restoration of miR-577 significantly suppressed the proliferation and colony formation and induced a G0/G1 cell cycle arrest in CRC cells. 5-Fluorouracil (5-FU)-resistant SW480 cells (SW480/5-FU) were found to have elevated levels of miR-577. Ectopic expression of miR-577 enhanced 5-FU sensitivity in SW480/5-FU cells. Heat shock protein 27 (HSP27) was identified as a target gene of miR-577. Enforced expression of HSP27 reversed the effects of miR-577 on CRC cell growth and 5-FU sensitivity. Xenograft tumors derived from miR-577-overexpressing SW480 cells exhibited significantly slower growth than control tumors. In conclusion, our results support that miR-577 acts as a tumor suppressor in CRC likely through targeting HSP27. Therefore, miR-577 may have therapeutic potential in the treatment of CRC.
Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Haiping
H
Jiang
Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Hui
H
Ju
Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Lin
L
Zhang
Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Haijun
H
Lu
Department of Medical Oncology, Qinghai People's Hospital, Xining, People's Republic of China.
Kan
K
Jie
D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002681:China; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D018832:Molecular Chaperones; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C000590091:MIRN577 microRNA, human; D035683:MicroRNAs; D018832:Molecular Chaperones; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D005472:Fluorouracil
HSP27; colorectal cancer; drug resistance; growth; miR-577