LINC00657 regulate colorectal carcinoma invasion and migration by enhancing heparanase expression through recruiting SMAD family member 2.

Long noncoding RNAs are master regulators of several cancer phenotypes, such as cell growth, apoptosis, and motility. This study is designed to resolve the relevance of LINC00657 with tumor invasion and migration and its action mechanism in colorectal carcinoma (CRC). LINC00657 and HPSE levels were first examined in cancerous tissues from CRC patients and CRC cells. Then functional experiments were conducted to evaluate the abilities of HCT116 and SW620 cells to proliferate, migrate, and invade when LINC00657 or HPSE was knocked down, or LINC00657 knockdown and SMAD2 overexpression were simultaneously introduced. Snail and E-cadherin levels in the CRC cells were evaluated. Next, the binding between LINC00657 and SMAD2 or between SMAD2 and HPSE was determined. LINC00657-silencing HCT116 cells were inoculated into nude mice, and the tumorigenesis and the levels of Snail and E-cadherin were evaluated. LINC00657 and HPSE were increasingly expressed in CRC. Knockdown of LINC00657 or HPSE inhibited the malignant properties of CRC cells, decreased Snail expression, and strengthened E-cadherin level. LINC00657 and HPSE could both bind to SMAD2. SMAD2 overexpression counteracted the inhibiting effect of LINC00657 silencing on HPSE expression and the growth and invasion of CRC cells. In vivo experiments further verified the suppression of LINC00657 knockdown on tumor growth and metastasis. LINC00657 recruits SMAD2 to HPSE promoter region to elevate HPSE transcription, thus accelerating CRC invasion and migration.