Circular RNA hsa_circ_0064559 affects tumor cell growth and progression of colorectal cancer

Abstract

Background Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. It is essential to identify new CRC-associated therapeutic targets and diagnostic biomarkers. Previous studies have demonstrated that a series of circular RNAs (circRNAs) play a crucial role in CRC pathogenesis. This study assessed the potential of hsa_circ_0064559 in tumor cell growth and progression of CRC. Methods Six pairs of matched CRC and normal colorectal tissue samples were sequenced using the Affymetrix Clariom D array. Using RNA interference, the expression of thirteen circRNAs was knocked down in CRC cells. The proliferation of CRC cell lines (RKO and SW620 cells) was detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Apoptosis and cell cycle were determined by flow-cytometric analysis. An in vivo study uses nude mice to establish a CRC mouse model. The differentially expressed genes were analyzed using Affymetrix primeview human GeneChip array and verified by polymerase chain reaction. Results Affymetrix Clariom D array analysis revealed that thirteen circRNAs were upregulated in CRC. The proliferation of CRC cell lines was decreased, while the proportion of apoptotic and G1 phase cells was higher after hsa_circ_0064559 knockdown. In vivo xenograft nude mice model revealed that the volume and weight of the tumor were reduced by hsa_circ_0064559 knockdown. In Affymetrix primeview human GeneChip array, we found six upregulated genes (STAT1, ATF2, TNFRSF10B, TGFBR2, BAX, and SQSTM1) and two downregulated genes (SLC4A7 and CD274) related to apoptosis and proliferation of colorectal cancer cells after hsa_circ_0064559 knockdown. Conclusions The hsa_circ_0064559 knockdown could inhibit the proliferation, promote apoptosis in CRC cell lines in vitro, and inhibit the development of CRC tumors in vivo. The mechanism may be related to activating a wide range of signaling pathways. The hsa_circ_0064559 may be a potential biomarker for early diagnosis or prognosis of CRC and a novel drug target for CRC therapy.

Functions of Circular RNA in Human Diseases and Illnesses

“…The expression of FGF2 ligand has improved by circWDR77 in smooth muscle cells found in vascular tissue [ 67 ]. Furthermore, a recent study found that the knockdown of hsa_circ_0064559 expanded apoptosis and reduced proliferation rate in cells found in colorectal cancer [ 68 ]. Collectively, this evidence shows that circRNAs have the ability to regulate cell proliferation by regulating various signaling pathways and thus can control important cellular processes.…”

Virus-Encoded Circular RNAs: Role and Significance in Viral Infections

“…Most studies have focused on circRNAs encoded by the cells at various stages of their life, during which they play innumerable and fundamental roles [57], such as miRNA sponges [58], regulation of cellular proliferation [59], protein-binding [60], splicing regulation [61] and roles in the immune system [62]. Due to their involvement in all these crucial functions, it is assumed that cellular circRNAs could have strong correlation with various diseases.…”