Circular RNAs (circRNAs) have been identified play a vital role in various different types of cancer via sponging miRNAs (microRNAs). However, their role in lung adenocarcinoma (LUAD) remains largely unclear. In this study, we systematically characterized the circRNA expression profiles in the LUAD cancer tissues and paired adjacent noncancerous tissues. Three circRNAs were found to be significantly upregulated. Among them, has-circRNA-002178 was further confirmed to be upregulated in the LUAD tissues, and LUAD cancer cells. Subsequently, we also found has-circRNA-002178 could enhance PDL1 expression via sponging miR-34 in cancer cells to induce T-cell exhaustion. More importantly, circRNA-002178 could be detected in exosomes of plasma from LUAD patients and could serve as biomarkers for LUAD early diagnosis. Finally, we found circRNA-002178 could be delivered into CD8 + T cells to induce PD1 expression via exosomes. Taken together, our study revealed that circRNA-002178 could act as a ceRNA to promote PDL1/PD1 expression in lung adenocarcinoma.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. miR-455-5p has increased expression and the ability to promote tumorigenesis in certain cancers. However, the role of miR-455-5p in NSCLC has not been sufficiently investigated. SOCS3 (suppressor of cytokine signaling 3), an important tumor suppressor, is often aberrantly inactivated in various tumors, but it is currently unclear whether SOCO3 is a target of miR-455-5p. In the present study, we investigated the role of miR-455-5p in NSCLC. We found that the expression of miR-455-5p was up-regulated in NSCLC tumor tissues compared to corresponding noncancerous tissues, and its expression was correlated with metastasis and tumor node metastasis in NSCLC tissue. We then showed that miR-455-5p promoted migration, invasion and proliferation in NSCLC cell lines. Additionally, we also found that SOCS3 was the direct target gene of miR-455-5p. Consistently, the expression of SOCS3 was negatively correlated with the expression of miR-455-5p in NSCLC tissues. We further show that aberrant miR-455-5p expression is partially controlled by activated ERK signaling in NSCLC. Therefore, miR-455-5p could enhance the growth and metastasis of NSCLC by inhibiting SOCS3, thus providing a potential molecular therapeutic target for the treatment of NSCLC patients.

Gastroesophageal reflux impairs the mucosal barrier in the distal esophagus, allowing chronic exposure of the squamous epithelium to multitudinous stimulations and inducing chronic inflammation. Esophagitis is a response to inflammation of the esophageal squamous mucosa. Our study clarified that alcohol accumulation could aggravate the progress of esophagitis by inducing pyroptosis; however, Ac-YVAD-CMK, an inhibitor of caspase-1, could effectively suppress the expression of IL-1β and IL-18 both in vivo and in vitro, reducing the inflammatory response, which is promised to be an agent to inhibit the progression of esophagitis. Additionally, caspase-1-derived pyroptosis is involved in esophageal cancer.

Many studies have shown that downregulation of miR-138 occurs in a variety of cancers including non-small cell lung cancer (NSCLC). However, the precise mechanisms of miR-138 in NSCLC have not been well clarified. In this study, we investigated the biological functions and molecular mechanisms of miR-138 in NSCLC cell lines, discussing whether it could turn out to be a therapeutic biomarker of NSCLC in the future. In our study, we found that miR-138 is downregulated in NSCLC tissues and cell lines. Moreover, the low level of miR-138 was associated with increased expression of SOX4 in NSCLC tissues and cell lines. Upregulation of miR-138 significantly inhibited proliferation of NSCLC cells. In addition, invasion and EMT of NSCLC cells were suppressed by overexpression of miR-138. However, downregulation of miR-138 promoted cell growth and metastasis of NSCLC cells. Bioinformatics analysis predicted that SOX4 was a potential target gene of miR-138. Next, luciferase reporter assay confirmed that miR-138 could directly target SOX4. Consistent with the effect of miR-138, downregulation of SOX4 by siRNA inhibited proliferation, invasion, and EMT of NSCLC cells. Overexpression of SOX4 in NSCLC cells partially reversed the effect of miR-138 mimic. In addition, decreased SOX4 expression could increase the level of miR-138 via upregulation of p53. Introduction of miR-138 dramatically inhibited growth, invasion, and EMT of NSCLC cells through a SOX4/p53 feedback loop.

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