Circ_0001686 knockdown suppresses tumorigenesis and enhances radiosensitivity in esophagus cancer through regulating miR-876–5p/SPIN1 axis

Esophageal cancer is one of the most common malignant tumors [1]. Although great progress has been made in esophageal cancer treatment, its prognosis is still unsatisfactory [2], [3]. Surgery, radiotherapy and chemotherapy are the main treatment strategies for esophageal cancer [4]. Radiotherapy is one of the main methods to constrain the progression of esophageal cancer. [5]. However, esophageal cancer is prone to radiotherapy resistance during radiotherapy, so its therapeutic effect is limited [6]. Therefore, it is urgent to reveal the molecular mechanism of esophageal cancer development and radioresistance, and find effective therapeutic targets to inhibit malignant development and improve the radiosensitivity of esophageal cancer.

Non-coding RNA (ncRNA) plays a pivotal role in the regulation of cellular biological function. As an endogenous ncRNAs, circular RNAs (circRNAs) are characterized by covalently linked 3 '-and 5′ -ends, and form a closed loop stable structure [7], [8]. At present, increasing research shows that circRNAs were abnormally expressed in many cancers, including esophageal cancer [9], For instance, circAKT3 silencing accelerated tumorigenesis of esophageal cancer by elevating proliferative and invasive capacities of esophageal cancer cells [10]. Additionally, the expression of circDUSP16 was increased in esophageal carcinoma and its deficiency repressed the progression of esophageal cancer [11]. However, the relationship between circRNAs and radioresistance of esophageal carcinoma is rarely studied. In recent literature, we found that circ_0001686 was highly expressed in radioresistant cells of esophageal carcinoma [12]. Circ_0001686 (located on chromosome 7: 24663284–24708279) is derived from membrane palmitoylated protein 6 (MPP6) linear mRNA. However, its function in esophageal cancer and its relationship with radiotherapy have not been reported. In addition, circ_0001686 was abnormally highly expressed in prostate cancer and promoted tumor cell growth and metastasis [13]. Herein, we further investigate the functional role and regulatory mechanism of circ_0001686 in the development and radiosensitivity of esophageal cancer.

Numerous studies have uncovered that circRNAs exert their functions by acting as microRNA (miRNA) sponges [14]. MiRNAs are small RNAs of 18–25 nucleotides that regulate cellular functions by binding to target genes [15]. MiR-876–5p has been shown to exert a tumor-suppressive role in many cancers, including lung cancer [16], hepatocellular carcinoma [17], cervical cancer [18] and colorectal cancer [19]. Moreover, the abundance of miR-876–5p was low in esophageal cancer, and its overexpression could restrain the progression of esophageal cancer [20]. However, the function of miR-876–5p in radioresistance of esophageal cancer and its specific mechanism are still unclear.

SPIN1, a member of the SPIN/SSTY family, is upregulated in a variety of tumors and promotes tumor progression [21]. Similarly, up-regulation of SPIN1 in esophageal cancer has also been reported [22], [23]. However, the correlation between miR-876–5p and SPIN1 has not been studied. In addition, SPIN1 has been found to be associated with radiosensitivity in esophageal cancer [24]. Hence, the mechanisms by which SPIN1 is involved in tumor development and the course of radiotherapy need further elucidation.

In this work, the function of circ_0001686 in tumorigenicity and radiosensitivity of esophageal cancer and its possible mechanism will be further explored, aiming to provide a new candidate target for esophageal cancer.

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