[ARTICLE WITHDRAWN] Upregulation of MicroRNA-935 Promotes the Malignant Behaviors of Pancreatic Carcinoma PANC-1 Cells via Targeting Inositol Polyphosphate 4-Phosphatase Type I Gene (INPP4A)

Abstract

Our goal was to determine the roles and regulatory mechanism of microRNA-935 (miR-935) in the progression of pancreatic cancer. The results showed that, compared with normal pancreatic tissues and cells, the expression of miR-935 was markedly upregulated, while INPP4A expression was obviously downregulated in pancreatic cancer tissues and PANC-1 cells. After transfection with the miR-935 inhibitor, miR-935 was significantly suppressed, and suppression of miR-935 significantly inhibited cell proliferation, suppressed cell migration, and induced cell apoptosis of pancreatic cancer cells. Moreover, suppression of miR-935 resulted in a significant increase in the expression of p27. Also, suppression of miR-935 resulted in significant expression changes of EMT markers; E-cadherin was significantly upregulated, while N-cadherin, Snail, and vimentin were markedly downregulated. In addition, after suppression of miR-935, the expression of apoptosis-related proteins was also changed; Bax was significantly upregulated while Bcl-2, procaspase 3, and active caspase 3 were obviously downregulated. Importantly, opposite effects were obtained when miR-935 was overexpressed by transfection with the miR-935 mimic. In addition, INPP4A was a direct target of miR-935. Silencing of INPP4A significantly counteracted the effects of miR-935 suppression on cell migration and apoptosis, as well as the expression changes of the above EMT- and apoptosis-related molecules. Our findings indicate that upregulation of miR-935 may promote pancreatic cancer cell proliferation and migration and inhibit cell apoptosis by targeting INPP4A. miR-935 and INPP4A may serve as potential targets in the therapy of pancreatic cancer.

<p>MiR-935 Promotes Clear Cell Renal Cell Carcinoma Migration and Invasion by Targeting IREB2</p>

“…31 As for miR-935, Wang et al found that miR-935 was upregulated in pancreatic carcinoma and targeted inositol polyphosphate 4-phosphatase type I to promote cancer malignant behavior. 18 Liu et al confirmed the truth that miR-935 could target SOX7 to promote liver cancer cell proliferation and migration. 19 Yang et al informed that miR-935 promoted cell proliferation by targeting SOX7 in gastric cancer.…”

“…15 Mature miRNA regulates gene expression negatively by repressing the translation of the target gene's proteins from messenger RNAs (mRNAs) or by binding to the 3ʹ-untranslated regions to increase the degradation of mRNAs. 16,17 Recently, miR-935 is observed to be upregulated in pancreatic cancer, 18 liver cancer 19 and gastric cancer. 20 However, the expression and potential roles of miR-935 in renal cancer progression are largely unknown.…”

MicroRNA-296-5p Promotes Cell Invasion and Drug Resistance by Targeting Bcl2-Related Ovarian Killer, Leading to a Poor Prognosis in Pancreatic Cancer

“…Zhang et al [31] showed that overexpression of miR-15b induced EMT by inhibiting SMURF2 in the pancreatic cancer cell line BxPC-3. Moreover, Wang et al showed that upregulation of miR-935 promoted EMT by inhibiting inositol polyphosphate 4-phosphatase type I gene in the pancreatic cancer cell line HPDE6-C7 [32]. However, these studies focused only on miR-15b and miR-935, respectively, and did not examine miRNA profiles in pancreatic cancer tissues or pancreatic cancer cell lines.…”

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

“…As a novel miRNA, the studies on miR-935 are not very abundant. miR-935 has been reported to be a prognostic biomarker of weight loss (10); furthermore, miR-935 has also been reported to be upregulated in cluster of differentiation133+ neural stem cells when compared with medulloblastoma specimens (11); in addition, upregulation of miR-935 promotes the malignant behaviors of PANC-1 pancreatic carcinoma cells through targeting inositol polyphosphate 4-phosphatase type I gene (12). However, its specific role and target gene in NSCLC have not been reported.…”