BRAF activated non-coding RNA (BANCR) promoting gastric cancer cells proliferation via regulation of NF-κB1

https://doi.org/10.1016/j.bbrc.2015.07.158Get rights and content

Highlights

  • BANCR up-regulated in gastric cancer (GC) tissues and cell lines MGC803 and BGC823.

  • Down-regulation of BANCR inhibited GC cell growth and promoted cell apoptosis.

  • Down-regulation of BANCR contributed to decreased 3′UTR of NF-κB1 and its expression.

  • Overexpressed NF-κB1 reversed the effect of BANCR on GC cell growth.

  • miR-9 inhibitor reversed the effect of BANCR on cancer GC cell growth.

Abstract

Background and objective

Long non-coding RNA, BANCR, has been demonstrated to contribute to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer is still unknown. In present study, we investigated whether BANCR was involved in the development of gastric cancer cells via regulation of NF-κB1.

Methods

Human gastric cancer tissues were isolated as well as human gastric cell lines MGC803 and BGC823 were cultured to investigate the role of BANCR in gastric cancer.

Results

BANCR expression was significantly up-regulated in gastric tumor tissues and gastric cell lines. Down-regulation of BANCR inhibited gastric cancer cell growth and promoted cell apoptosis, and it also contributed to a significant decrease of NF-κB1 (P50/105) expression and 3′UTR of NF-κB1 activity. Overexpression of NF-κB1 reversed the effect of BANCR on cancer cell growth and apoptosis. MiroRNA-9 (miR-9) targeted NF-κB1, and miR-9 inhibitor also reversed the effects of BANCR on gastric cancer cell growth and apoptosis.

Conclusion

BANCR was highly expressed both in gastric tumor tissues and in cancer cells. NF-κB1 and miR-9 were involved in the role of BANCR in gastric cancer cell growth and apoptosis.

Introduction

Gastric cancer is one of the most common cause of death from cancer worldwide [1]. It has been demonstrated that genetic components and environmental factors contribute to the progression of the gastric cancer [2], [3]. Despite the 5- year relative survival rate is increased to about two times, the survival rate of the patients is still low with less than 30% in United States [4], due to the advanced stage of the disease at the time of diagnosis. Therefore, it is an urgent need to demonstrate the regulatory network underlying the development of gastric cancer to explore the efficient or reliable biomarkers for early diagnosis and targeted therapy.

Long non-coding RNAs (long ncRNAs, lncRNAs), longer than 200 nucleotides, are non-protein coding transcripts [5] with the functions to regulate gene expression at the level of chromatin modification, transcription and post-transcriptional processing [6]. BRAF-activated non-coding RNA (BANCR), a 693-bp lncRNA on chromosome 9 is reported to be involved in malignant melanoma [7], lung carcinoma [8] and papillary thyroid carcinoma [9]. BANCR contributes to the proliferation and migration of tumors, which is a potential marker to explain the pathological physiology of tumor formation and a target site to the treatment of cancers. Recently, Li et al. has demonstrated that high expression of BANCR is an independent unfavorable prognostic factor in gastric cancer patients [10]. Even so, very few reports have been demonstrated in gastric cancer. In addition, the mechanism of BANCR underlying gastric cancer is needed to be deeply explored.

MicroRNAs (miRNAs) are small non-coding RNA molecules acting as RNA silencing and post-transcriptional regulation of gene expression. MiR-9 has been demonstrated to play a critical role in the proliferation, invasion and metastasis of various cancers [11], [12], [13], including gastric cancer [14], [15]. The NF-κB1 (P50/105) gene takes part in the regulation of immune responses, cell-cycle progression and oncogenesis [16], [17]. In addition, NF-κB1 expression has been indicated to be mediated by miR-9 in cancers [18], [19]. In present study, we speculated that BANCR probably was involved in the development of gastric cancer cells via NF-κB1 regulation mediated by miR-9.

Section snippets

Specimen collection

Thirty pairs of gastric specimen, including thirty human gastric adenocarcinoma tissues and thirty adjacent tissues, were obtained from the Affiliated Hospital of Jining Medical University. This study was approved by the Ethics Committee of Affiliated Hospital of Jining Medical University. Written informed consents were obtained from all participants.

Cell culture

Human gastric cancer cell lines BGC823 and SGC7901 were purchased from the Type Culture Collection of the Chinese Academy of Sciences (Shanghai,

BANCR expression was up-regulated in gastric cancer

The BANCR expression was first investigated in gastric cancer. As shown in Fig. 1A, the BANCR level in human gastric cancer tissue was almost 5 folds of matched normal gastric tissue. In gastric cancer cells, the elevated BANCR expression was also observed in BGC-823 and MGC-803 cells compared with GES-1 cells (Fig. 1B).

The effects and mechanism of BANCR expression on gastric cancer cell proliferation and apoptosis

To demonstrate the role of BANCR in gastric cancer cell proliferation and apoptosis, a shRNA-323 (LV-BANCR-323) or shRNA-540 (LV-BANCR-540) was transfected into BGC-823 and

Discussion

lncRNAs are newly recognized regulators involved in the human pathophysiologic processes, including oncogenesis [20], [21]. The researches about the mechanisms of lncRNAs on onset and development of diseases are severely limited. In present study, we found that the BANCR expression level was highly expressed in gastric cancer tissues and gastric cancer cells, and miR-9 mediating NF-κB1 participated in the proliferation of cancer cell by BANCR regulation.

BANCR has been indicated to be abnormally

Conflict of interest

All authors declare that there is no conflict of interest.

Acknowledgment

This work is funded by 973 Program (2011CB504302), National Nature Science Foundation of China (30872318) and Scientific and Technological Development Plan of Shandong Province (2010GW20237).

References (25)

  • T.R. Mercer et al.

    Long non-coding RNAs: insights into functions

    Nat. Rev. Genet.

    (2009)
  • R. Li

    Long non-coding RNA BANCR promotes proliferation in malignant melanoma by regulating MAPK pathway activation

    PLoS One

    (2014)
  • Cited by (74)

    • GANLDA: Graph attention network for lncRNA-disease associations prediction

      2022, Neurocomputing
      Citation Excerpt :

      It has been shown that TUSC7 ranked at top 3 is down-regulated in gastric cancer samples [48]. It has been discovered that the expression of BANCR ranked at top 4 is significantly up-regulated in gastric tumor tissues and gastric cell lines [49]. It has been demonstrated that the TINCR ranked at top 5 is the target of miR-375 and can inhibit its expression in gastric cancer cells [50].

    • Transposons: Unexpected players in cancer

      2022, Gene
      Citation Excerpt :

      Furthermore, antidrug resistance mediated by AFAP1-AS1 was reported in breast cancer (Han et al., 2020). Other oncogenic lncRNAs whose expression is promoted by LTRs include BACE1 and HULC in liver and breast cancer (Gavgani et al., 2020; Li et al., 2015b; Liu et al., 2021; Yeganeh et al., 2020), UAC1 in TNBC and urothelial cancer (Hu et al., 2016; Jiang and Upton, 2019b; Li et al., 2015b), SAMMSON in melanoma (Leucci et al., 2016) and BANCR in gastric cancer (Zhang et al., 2015). TEs make the cancer cells vulnerable to immune-mediated clearance through activation of interferon signaling (Roulois et al., 2015).

    • Non-coding RNAs and potential therapeutic targeting in cancer

      2021, Biochimica et Biophysica Acta - Reviews on Cancer
    View all citing articles on Scopus
    View full text