Biochemical and Biophysical Research Communications
A novel lncRNA LOC101927746 accelerates progression of colorectal cancer via inhibiting miR-584-3p and activating SSRP1
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)
- et al.
Colorectal cancer
Lancet
(2014) Colorectal carcinoma: diagnostic, prognostic, and molecular features
Mod. Pathol.
(2003)- et al.
LncRNA MAFG-AS1 promotes the progression of colorectal cancer by sponging miR-147b and activation of NDUFA4
Biochem. Biophys. Res. Commun.
(2018) - et al.
Role of long noncoding RNA 799 in the metastasis of cervical cancer through upregulation of TBL1XR1 expression
Mol. Ther. Nucleic Acids
(2018) - et al.
A novel lncRNA, LINC00460, affects cell proliferation and apoptosis by regulating KLF2 and CUL4A expression in colorectal cancer
Mol. Ther. Nucleic Acids
(2018) - et al.
LncRNA HAND2-AS1 sponging miR-1275 suppresses colorectal cancer progression by upregulating KLF14
Biochem. Biophys. Res. Commun.
(2018) - et al.
Long noncoding RNA TMEM75 promotes colorectal cancer progression by activation of SIM2
Gene
(2018) - et al.
LncRNA TUG1 promoted KIAA1199 expression via miR-600 to accelerate cell metastasis and epithelial-mesenchymal transition in colorectal cancer
J. Exp. Clin. Canc. Res.
(2018) - et al.
Blockage of SSRP1/Ets-1/Pim-3 signalling enhances chemosensitivity of nasopharyngeal carcinoma to docetaxel in vitro
Biomed. Pharmacother.
(2016) - et al.
SSRP1 contributes to the malignancy of hepatocellular carcinoma and is negatively regulated by mir-497
Mol. Ther.
(2016)
Cancer statistics
Ca - Cancer J. Clin.
LncRNA NEAT1 Promotes the Tumorigenesis of Colorectal Cancer by Sponging MiR-193a-3p
Landscape of transcription in human cells
Nature
LncKdm2b controls self-renewal of embryonic stem cells via activating expression of transcription factor Zbtb3
EMBO J.
Long noncoding RNA lncKdm2b is required for ILC3 maintenance by initiation of Zfp292 expression
Nat. Immunol.
LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells
Nat. Commun.
Long non-coding RNA UCA1 increases chemoresistance of bladder cancer cells by regulating Wnt signaling
FEBS J.
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