Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis

Abstract

Background Long non-coding RNAs (lncRNA) are reported to influence colorectal cancer (CRC) progression. Currently, the functions of the lncRNA ZNF561 antisense RNA 1 (ZNF561-AS1) in CRC are unknown. Methods ZNF561-AS1 and SRSF6 expression in CRC patient samples and CRC cell lines was evaluated through TCGA database analysis, western blot along with real-time PCR. SRSF6 expression in CRC cells was also examined upon ZNF561-AS1 depletion or overexpression. Interaction between miR-26a-3p, miR-128-5p, ZNF561-AS1, and SRSF6 was examined by dual luciferase reporter assay, as well as RNA binding protein immunoprecipitation (RIP) assay. Small interfering RNA (siRNA) mediated knockdown experiments were performed to assess the role of ZNF561-AS1 and SRSF6 in the proliferative actives and apoptosis rate of CRC cells. A mouse xenograft model was employed to assess tumor growth upon ZNF561-AS1 knockdown and SRSF6 rescue. Results We find that ZNF561-AS1 and SRSF6 were upregulated in CRC patient tissues. ZNF561-AS1 expression was reduced in tissues from treated CRC patients but upregulated in CRC tissues from relapsed patients. SRSF6 expression was suppressed and enhanced by ZNF561-AS1 depletion and overexpression, respectively. Mechanistically, ZNF561-AS1 regulated SRSF6 expression by sponging miR-26a-3p and miR-128-5p. ZNF561-AS1-miR-26a-3p/miR-128-5p-SRSF6 axis was required for CRC proliferation and survival. ZNF561-AS1 knockdown suppressed CRC cell proliferation and triggered apoptosis. ZNF561-AS1 depletion suppressed the growth of tumors in a model of a nude mouse xenograft. Similar observations were made upon SRSF6 depletion. SRSF6 overexpression reversed the inhibitory activities of ZNF561-AS1 in vivo, as well as in vitro. Conclusion In summary, we find that ZNF561-AS1 promotes CRC progression via the miR-26a-3p/miR-128-5p-SRSF6 axis. This study reveals new perspectives into the role of ZNF561-AS1 in CRC.

A Signature of Nine lncRNA Methylated Genes Predicts Survival in Patients With Glioma

“…LncRNA is a type of RNA that is longer than 200 nucleotides and lacks protein-coding ability (6). Nevertheless, lncRNAs still play an extremely broad role in important life activities of organisms, including epigenetic modification of genes, splicing and editing of RNA, regulation of miRNA, and folding of protein molecules (7,8). Aberrant expression of lncRNAs has been observed in human cancers, where they can act as either tumor suppressor genes or oncogenes, depending on the environment in which tumor cells are located (9,10).…”

Identification and verification of m7G-Related genes as biomarkers for prognosis of sarcoma

“…MiR-128-5p participated in the progression of colorectal cancer (Si et al, 2021). Our study revealed that these miRNAs and lncRNAs were related to the prognosis of sarcoma patients.…”

Targeting Splicing Factor SRSF6 for Cancer Therapy

“…Furthermore, SRSF6 overexpression is significantly associated with poor overall survival (Wan et al, 2019). Park et al showed that SRSF6 protein was overexpressed in a cohort of colorectal patients by Western blot (Park et al, 2016), which was further confirmed in another study by Western blot (Si et al, 2021). However, Lin et al showed that SRSF6 protein was downregulated in colorectal cancer tissues in eight patients compared with adjacent normal tissues by Western blot (Lin et al, 2017).…”

“…circFBXL5 functions as a ceRNA to sponge miR-660 and upregulate SRSF6 expression in breast cancer ( Zhou et al, 2020a ). Another example is that lncRNA ZNF561-AS1 can sponge miR-26a-3p and miR-128-5p to upregulate SRSF6 expression in colorectal cancer ( Si et al, 2021 ).…”