Abstract
BackgroundLong 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.MethodsZNF561-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.ResultsWe 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.ConclusionIn 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.
Highlights
Long non-coding RNAs are reported to influence colorectal cancer (CRC) progression
Analysis of ZNF561-AS1 level in various CRC cell lines consisting of SW620, HCT-116, HT-29, SW480, SW48 and LoVo cells showed that ZNF561AS1 expression was increased in all CRC cell lines compared to non-malignant human colon epithelial cell line, CCD841 CoN (Fig. 1c), with HCT-116 expressing the highest ZNF561-AS1 levels
We found that compared to CRC samples from untreated patients, samples from patients treated with chemotherapy exhibited lower ZNF561-AS1 levels (Fig. 1d)
Summary
Long non-coding RNAs (lncRNA) are reported to influence colorectal cancer (CRC) progression. The functions of the lncRNA ZNF561 antisense RNA 1 (ZNF561-AS1) in CRC are unknown. Long non-coding RNAs (lncRNAs) are composed of > 200 nucleotides reported to influence various disorders [3,4,5], including cancers [6,7,8], by adsorbing miRNAs [9], mediating DNA interactions [10], and binding to proteins as decoys [11]. Many lncRNAs are show abnormal expression in CRC which affects its progression and drug resistance [12,13,14]. Exosomal lncRNA H19 confers CRC cells stemness and chemo-resistance [17]. Since lncRNAs influence CRC progression, their identification and understanding of their biological functions in CRC are imperative as they have anti-CRC therapeutic value
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