Circular RNA circ_103820 suppresses lung cancer tumorigenesis by sponging miR-200b-3p to release LATS2 and SOCS6

Abstract

A growing number of circular RNAs (circRNAs) have been identified and verified in several cancers. However, highly efficient therapeutic methods based on circRNAs in lung cancer remain largely unexplored. In the present study, we identified a novel circular RNA, hsa_circ_103820, based on Gene Expression Omnibus (GEO) data. Functionally, overexpression of hsa_circ_103820 showed significant inhibitory effects on the proliferation, migration and invasion of lung cancer cells, and knockdown of hsa_circ_103820 played promoting roles. Regarding the mechanism, we revealed that miR-200b-3p was a direct target of hsa_circ_103820 and that LATS2 and SOCS6 were the downstream target genes of miR-200b-3p. Therefore, we identified a novel potential tumor suppressive function of hsa_circ_103820 in lung cancer.

Regulatory functions of miR‑200b‑3p in tumor development (Review)

“…For instance, in most cases, it exhibits tumor-suppressive effects and is therefore downregulated, with examples of such tumors being colorectal cancer (CRC) (4-7), hepatocellular carcinoma (HCC) (8)(9)(10)(11)(12), pancreatic cancer (13,14), gastrointestinal stromal tumors (15), breast cancer (16)(17)(18), melanoma (19), glioblastoma (20), glioma (21), thyroid carcinoma (22), cemento-ossifying fibroma (23), esophageal cancer (24,25), oral squamous cell carcinoma (26), prostate cancer (27,28), renal cell carcinoma (29), bladder cancer (30), and malignant mesothelioma (31). However, as already noted, this microRNA can also be oncogenic in various types of cancers, with examples of such tumors being prostate cancer (32,33), lung cancer (34)(35)(36)(37)(38), oral squamous cell carcinoma (39), esophageal squamous cell carcinoma (40), breast cancer (41), colorectal cancer (42,43), neck cancer (44), cholangiocarcinoma (45), and hepatocellular carcinoma (46). Table I and Fig.…”

“…miR-200b-3p and its functions in lung cancer. In the case of lung cancer, miR-200b-3p mainly acts as an oncogene by regulating the expression of the ATP-binding cassette transporter A member 1 (ABCA1) (34), the transcriptional intermediary factor 1 γ (TIF1γ) (35), the large tumor suppressor kinase 2 (LATS2) as well as the suppressor of cytokine signaling 6 (SOCS6) (36), all of which are involved in tumor progression. Among these, the tumor-suppressor gene ABCA1 encodes a transmembrane protein that transports cholesterol to the outside of the cell and a study by Liu et al demonstrated that, by acting on this gene, miR-200b-3p could encourage non-small-cell lung cancer to grow and metastasize (34).…”

“…Similarly, TIF1γ, also known as tripartite motif-containing 33 (TRIM33), inhibits tumorigenesis and proliferation by degrading β-catenin, a key component of the Wnt pathway but when miR-200b-3p targets this gene, TGF-β-induced EMT is promoted along with tumor invasion (35). Finally, even though both LATS2 and SOCS6 act as tumor suppressors in various tumors, the upstream miR-200b-3p can regulate their expression to promote the proliferation of lung cancer as well as metastasis (36).…”

Role of circular RNAs in the diagnosis, regulation of drug resistance and prognosis of lung cancer (Review)

“…Cell experiments revealed that high circ_0000079 expression inhibited cisplatin resistance in A549/DDP and H460/DDP cells, implying that circ_0000079 could be used as a prognostic indicator and therapeutic target for NSCLC. Chi et al ( 92 ) showed that overexpression of hsa_circ_103820 significantly inhibited the proliferation, migration and invasion of lung cancer cells, while knockdown of hsa_circ_103820 played a tumorigenic role. These results suggested that hsa_circ_103820 has a potential novel function as a tumor suppressor in lung cancer.…”

LINC01088 regulates the miR-95/LATS2 pathway through the ceRNA mechanism to inhibit the growth, invasion and migration of gastric cancer cells

“…28 According to studies, the LATS2 gene is located at chromosome 13q12.11 and has the tumor suppressor gene functions; its expression is downregulated in lung cancer, prostate cancer, and GC, and has an inhibitory influence on tumor development. [29][30][31] LATS2 expression was discovered to be decreased in GC cells, and LATS2 overexpression in cells prevented cell invasion and migration and altered the expression of associated genes and proteins. These findings suggest that the LATS2 gene, as a tumor suppressor gene, has a strong inhibitory effect on GC cell invasion; however, the specific mechanism of action still needs to be explored in depth.…”