Abstract
Long noncoding RNAs (lncRNAs) have been confirmed, which are involved in tumorigenesis and metastasis in colorectal cancer (CRC). FOXC2 antisense RNA 1 (FOXC2-AS1) was reported, facilitating the proliferation and progression in several cancers. However, the role of FOXC2-AS1 in CRC cell migration and metastasis is not unclear. In this study, we observed that lncRNA FOXC2-AS1 was upregulated in CRC tissues, and its high expression indicated the poor survival in CRC patients. Meanwhile, FOXC2-AS1 was higher in CRC tissues with metastasis than that of nonmetastatic tumor tissues. We found that FOXC2-AS1 was predominately expressed in the nucleus of tissues and cells. FOXC2-AS1 knockdown suppressed CRC cell growth, invasion, and metastasis in vitro and in vivo. Moreover, FOXC2-AS1 could positively regulate the neighboring gene FOXC2 and stabilized FOXC2 mRNA by forming a RNA duplex. Meanwhile, ectopic expression of FOXC2 could obviously alleviate the suppressed effects caused by silencing FOXC2-AS1. For the mechanism, FOXC2-AS1 knockdown could reduce intracellular Ca2+ levels, inhibited FA formation and FAK signaling, and these suppressed effects were mitigated by increasing FOXC2 expression. These results demonstrated that FOXC2-AS1 enhances FOXC2 mRNA stability to promote CRC proliferation, migration, and invasion by activation of Ca2+-FAK signaling, which implicates that FOXC2-AS1 may represent a latent effective therapeutic target for CRC progression.
Highlights
Colorectal cancer (CRC) is a common digestive tract malignancy, accounting for about 40% new tumors of the digestive tract
forkhead box protein C2 (FOXC2)-AS1 is upregulated in CRC tissues and predicts poor prognosis In 66 CRC and 15 adjacent normal tissues, FOXC2-AS1 expression was elevated in CRC tissues by qRT-PCR assay (Fig. 1a)
FOXC2-AS1 had a higher expression in CRC tissues with metastasis than nonmetastatic tumor tissues (Fig. 1b)
Summary
Colorectal cancer (CRC) is a common digestive tract malignancy, accounting for about 40% new tumors of the digestive tract. There were nearly 1.3 million new CRC cases and more than 0.6 million deaths worldwide every year[1]. Remarkable progress has been made in CRC treatment, but over half of the patients with advanced CRC die from recurrence and metastasis, which led to the unfavorable prognosis[2,3]. A better illustration of the molecular mechanisms regarding CRC progression is urgently needed. Long noncoding RNAs (lncRNAs) are a kind of RNA transcripts with lengths >200 nt, and limit or lack protein-. HOTAIR, etc., were widely reported to be involved in human tumorigenesis and metastasis[8,9,10].
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