Knockdown of miR‑935 increases paclitaxel sensitivity via regulation of SOX7 in non‑small‑cell lung cancer

Abstract

Sex determining region Y‑box (SOX)7 is a member of the SOX family and is responsible for various developmental processes. As a tumor suppressor, decreased expression of SOX7 has been observed in several cancer types, including non‑small‑cell lung cancer (NSCLC). However, the mechanism underlying SOX7 downregulation and its role in chemoresistance in NSCLC remains poorly understood. In the present study, the inhibition of microRNA (miR)‑935 increased the expression of SOX7 at the mRNA and protein levels in A549 cells. The luciferase reporter assay verified that miR‑935 could directly bind to the 3'untranslated region of SOX7 mRNA to suppress its expression in A549 cells. In addition, the inhibition of miR‑935 enhanced the anticancer effect of paclitaxel, i.e., induced cell growth arrest and apoptosis in A549 cells. It was further observed that the inhibition of miR‑935 decreased the B cell lymphoma (Bcl)‑2 and phosphorylated‑RAC‑α serine/threonine‑protein kinase (AKT) protein levels and increased the Bcl‑2 associated X, apoptosis regulator protein levels, without affecting the AKT levels in the presence of paclitaxel within A549 cells. The findings of the present study validate miR‑935 as a predictor of paclitaxel sensitivity in NSCLC.

miR-935 Inhibits Oral Squamous Cell Carcinoma and Targets Inositol Polyphosphate-4-phosphatase Type IA (INPP4A)

“…Conversely, miR-935 is reported as an onco-miR in gastric cancer that inhibits SOX7 (55), in non-small cell lung cancer that inhibits IL-27 (41), in non-small-cell lung cancer that inhibits SOX7 (56), in hepatocellular carcinoma that inhibits SOX7 and activates c-Myc and cyclin D1 (57), in pancreatic carcinoma that inhibits INPP4A and possibly p27 (58), and in colorectal cancer that targets INPP4A (59). In addition, overexpression of miR-935 has been reported in stathmindepleted neuroblastoma (60), Helicobacter pylori-positive gastric cancer (using Gene Expression Omnibus database) (61), stage-I endometrioid endometrial cancer (62), bladder cancer (63), and chronic hepatitis B that progressed to cirrhosis/hepatocellular carcinoma (64).…”

Hsa_circ_0002483 inhibited the progression and enhanced the Taxol sensitivity of non-small cell lung cancer by targeting miR-182-5p

“…Although the molecular mechanisms underlying Taxol resistance have not yet been fully elucidated, emerging evidence has shown that miRNAs and lncRNAs play a critical role in the Taxol resistance of NSCLC 29,30 . The roles of circRNAs in the Taxol resistance of NSCLC have barely been investigated.…”

Role of SOX Protein Groups F and H in Lung Cancer Progression

“…Another miRNA molecule proved to have binding properties to the 3'UTR region of the SOX7 transcript is miR-935. miR-935 has already been reported to downregulate SOX7 expression in liver, gastric and lung cancers [86,105,106]. Downregulation of SOX7 via miR-935 promotes cell invasion and cell proliferation, as well as cell apoptosis in all the aforementioned types of cancer.…”

“…It has been observed that miR-935 was clearly upregulated in NSCLC tissues compared to non-malignant lung tissue. Knockdown of miR-935 resulting in an increased SOX7 expression leads to the promotion of cell proliferation arrest and cell apoptosis of the lung cancer adenocarcinoma cell line A549 [105]. This could be due to the reduction in the expression level of the Bcl-2 protein and the activity of p-Akt, resulting in an increase in the expression of the proapoptotic Bax protein.…”