Hsa_Circ_0001947/MiR-661/DOK7 Axis Restrains Non-Small Cell Lung Cancer Development

Abstract

Hsa_circ_0001947 is associated with multiple cancers, but its function in non-small cell lung cancer (NSCLC) is ambiguous and needs further research. The targeting relationship among circ_0001947, miR-661, and downstream of tyrosine kinase 7 (DOK7) was predicted by database and further verified by dual-luciferase reporter assay, while their expressions in cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After transfection, cell biological behaviors and expressions of miRNAs, miR-661 and DOK7 were determined by cell function experiments and qRT-PCR, respectively. Circ_0001947 was low-expressed in NSCLC tissues and cells. Circ_0001947 knockdown intensified cell viability and proliferation, induced cell cycle arrest at S phase, suppressed apoptosis and evidently enhanced miR-510, miR-587, miR-661 and miR-942 levels, while circ_0001947 overexpression did the opposite. MiR-661 was a target gene of circ_0001947 that participated in the regulation of circ_0001947 on cell biological behaviors. Furthermore, DOK7, the target gene of miR-661, partly participated in the regulation of miR-661 on cell viability. Hsa_circ_0001947 acts as a sponge of miR-661 to repress NSCLC development by elevating the expression of DOK7.

DOK7, a target of miR-299-5p, suppresses the progression of bladder cancer

“…We further showed that DOK7 serves as a negative regulator of JAK signaling pathway in BLCA cells. In agreement with our data, DOK7 was reported as a tumor suppressor in glioma, breast and lung cancer [19,20,[30][31][32][33]. For example, DOK7 was found to be down-regulated in lung cancer and its reduced expression was associated with the poor survival in lung cancer patients [30][31][32].…”

“…In agreement with our data, DOK7 was reported as a tumor suppressor in glioma, breast and lung cancer [19,20,[30][31][32][33]. For example, DOK7 was found to be down-regulated in lung cancer and its reduced expression was associated with the poor survival in lung cancer patients [30][31][32]. In breast cancer, DOK7 suppresses the cell growth and mobility by targeting PI3K/AKT pathway [20].…”

ALKBH5/YTHDF2‐mediated m6A modification of circAFF2 enhances radiosensitivity of colorectal cancer by inhibiting Cullin neddylation

“…It has been found that circAFF2 plays different roles in different tumours. For example, circAFF2 was downregulated in non‐small cell lung cancer, 40 and acted as a sponge for miR‐661, inhibiting tumour progression by enhancing the expression of DOK7 40 . In gastric cancer, circAFF2 upregulates ANTXR 1 expression by adsorbing miR‐6894‐5p, thereby promoting tumour proliferation 41 .…”

“…For example, circAFF2 was downregulated in non‐small cell lung cancer, 40 and acted as a sponge for miR‐661, inhibiting tumour progression by enhancing the expression of DOK7. 40 In gastric cancer, circAFF2 upregulates ANTXR 1 expression by adsorbing miR‐6894‐5p, thereby promoting tumour proliferation. 41 Additionally, circAFF2 is highly expressed in renal cell carcinoma (RCC), and high expression patients with RCC had a poor prognosis.…”

Circ_0001947 promotes cell proliferation, invasion, migration and inflammation and inhibits apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes through miR-671-5p/STAT3 axis

“…Previous studies have shown that the dysregulation of circ_0001947 is linked to the development of NSCLC [ 2 ], gastric cancer [ 4 ] and acute myeloid leukemia [ 12 ]. Moreover, Qu et al and Zhi et al demonstrated that circ-AFF2 is highly expressed in RA and aggravated RA-FLS growth, inflammation, invasion and migration via regulating miR-650/CNP axis and miR-375/TAB2 axis [ 23 , 33 ].…”