A novel lncRNA LOC101927746 accelerates progression of colorectal cancer via inhibiting miR-584-3p and activating SSRP1

https://doi.org/10.1016/j.bbrc.2018.12.174Get rights and content

Highlights

  • Elevated expression of LOC101927746 is correlated with CRC progression.

  • LOC101927746 silencing suppresses CRC cell proliferation, migration and invasion.

  • LOC101927746 interacts with miR-584-3p which targets SSRP1.

  • LOC101927746/miR-584-3p/SSRP1 pathway modulates CRC progression.

Abstract

An increasing number of reports have indicated that long noncoding RNAs (lncRNAs) are involved in the pathogenesis of colorectal cancer (CRC). However, many lncRNAs remain unidentified in CRC, and their functions are yet to be elucidated. In this study, we investigated the function of lncRNA LOC101927746 in CRC progression. We found that LOC101927746 expression was significantly increased in CRC tissues according to the GEO dataset. Moreover, LOC101927746 expression was positively correlated with tumor stage and metastasis. Additionally, the high expression of LOC101927746 predicted poor prognosis in CRC patients. Functionally, we demonstrated that LOC101927746 silencing significantly suppressed the proliferation, migration, and invasion of CRC cells. In terms of its mechanism, LOC101927746 could serve as a competing endogenous RNA to inhibit miR-584-3p and activate its target gene SSRP1. The expression of miR-584-3p was inversely correlated with either LOC101927746 or SSRP1 in CRC tissues. The overexpression of SSRP1 or inhibition of miR-584-3p could reverse the effects of LOC101927746 knockdown in CRC cells. Taken together, our results suggest that the LOC101927746/miR-584-3p/SSRP1 axis modulates CRC progression.

Introduction

Colorectal cancer (CRC) is one of the most prevalent and aggressive cancers around the world [1]. Every year, over 1 million patients are diagnosed with CRC, and approximately half of these patients die [2]. Although improvements have been made on surgery and radiotherapy or chemotherapy in previous years, the outcomes of CRC patients still remain unfavorable. A major reason is that most patients are diagnosed at an advanced stage [3]. Moreover, tumor metastasis considerably increases its recurrence rate [4]. CRC is induced by complicated factors, such as genetic mutation [3]. The detailed mechanism regulating CRC development remains vague. Thus, more efforts are urgently required to study CRC progression.

Long noncoding RNAs (lncRNAs) are identified as noncoding RNA molecules with over 200 nucleotides in length [5]. In the past 10 years, a growing number of researchers have found that lncRNAs play pivotal physiological and pathological functions, including embryonic development, immune regulation, and tumorigenesis, by acting as signals or scaffolds [[6], [7], [8], [9]]. Particularly, the roles of lncRNAs in regulating tumor cell proliferation, survival, differentiation, and invasion have been widely studied [10]. For example, lncRNA Z38 promotes the growth and invasion of gastric cancer cells [11]. LncRNA AFAP1-AS1 promotes nasopharyngeal carcinoma growth and invasion by inhibiting miR-423-5p to regulate the Rho/Rac pathway [12]. LncRNA LOC100132354 promotes lung cancer progression via VEGFA/VEGFR2 signaling pathway-induced angiogenesis [13]. Additionally, lncRNA can serve as biomarkers for tumor diagnosis and prognosis [14,15]. The roles of lncRNA in CRC have also been acknowledged [3,16,17]. Hence, exploring how lncRNA regulates CRC progression is meaningful.

To date, the function of LOC101927746 has not been elucidated. The aim of our study is to determine the physiological function of LOC101927746 in CRC. We showed that LOC101927746 was upregulated in CRC tissues and correlated with tumor stage and metastasis. In addition, LOC101927746 might serve as a prognostic biomarker. Functionally, LOC101927746 promoted CRC progression through the miR-584-3p/SSRP1 axis. In conclusion, our study shows that the LOC101927746/miR-584-3p/SSRP1 signaling pathway regulates CRC development.

Section snippets

Clinical samples

Fifty-eight CRC tissues and 25 adjacent normal tissues were obtained from The First Affiliated Hospital of Wenzhou Medical University. This study was approved by the hospital's research ethics board. Written informed consents were signed by each patient. Tumor tissues were stored using liquid nitrogen.

Cell culture

Human CRC cell lines (HCT116, HT29, SW480, and LoVo) and normal colon epithelial cell line NCM460 were obtained from the Chinese Academy of Sciences (Shanghai, China). These cells were cultured

Elevated expression of LOC101927746 is correlated with CRC progression

We investigated the upregulated lncRNAs in CRC tissues according to the dataset GSE109454 to identify important lncRNAs involved in CRC progression. Among all upregulated lncRNAs in CRC tissues, lncRNA LOC101927746 ranked top and attracted our attention (Fig. 1A). The function of LOC101927746 in CRC remains fully unknown. qRT-PCR analysis validated its overexpression in CRC tissues (Fig. 1B). Additionally, in 25 pairs of CRC and normal tissues, LOC101927746 level was increased in most CRC

Discussion

The roles of LOC101927746 have not been reported previously. Herein, we showed that LOC101927746 expression was increased in CRC tissues and related with tumor stage, metastasis, and overall survival. Thus, LOC101927746 was a prognostic biomarker for CRC patients. We also performed a series of experiments to demonstrate that LOC101927746 plays oncogenic roles in the regulation of CRC cell proliferation, migration, and invasion.

Increasing evidence has demonstrated that lncRNAs exert essential

Conflicts of interest

None.

Acknowledgements

This study was supported by Zhejiang Provincial Natural Science Foundation of China (LY15H160058).

References (34)

  • R.L. Siegel et al.

    Cancer statistics

    Ca - Cancer J. Clin.

    (2015)
  • H.M. Yu et al.

    LncRNA NEAT1 Promotes the Tumorigenesis of Colorectal Cancer by Sponging MiR-193a-3p

    (2018)
  • S. Djebali et al.

    Landscape of transcription in human cells

    Nature

    (2012)
  • B. Ye et al.

    LncKdm2b controls self-renewal of embryonic stem cells via activating expression of transcription factor Zbtb3

    EMBO J.

    (2018)
  • B. Liu et al.

    Long noncoding RNA lncKdm2b is required for ILC3 maintenance by initiation of Zfp292 expression

    Nat. Immunol.

    (2017)
  • P. Zhu et al.

    LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells

    Nat. Commun.

    (2016)
  • Y. Fan et al.

    Long non-coding RNA UCA1 increases chemoresistance of bladder cancer cells by regulating Wnt signaling

    FEBS J.

    (2014)
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