piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity

Abstract

Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has recently been recognized, studies on the role and functional mechanism of piRNAs in lung adenocarcinoma (LUAD) development and progression are limited. In this study, we identified 10 differently expressed piRNAs in LUAD tissues compared to normal tissues, among which, piR-hsa-211106 expression levels were downregulated in LUAD tissues and cell lines. Furthermore, the effects of piR-hsa-211106 on the malignant phenotypes and chemosensitivity of LUAD cells were detected by gain- and loss-of-function analyses in vitro and in vivo, which showed that piR-hsa-211106 inhibited LUAD cell proliferation, tumor growth, and migration, but promoted apoptosis. Moreover, our finding indicated that piR-hsa-211106 is a potential therapeutic target that synergistically imparts anticancer effects with a chemotherapeutic agent for LUAD-cisplatin. Further mechanistic investigation indicated that piR-hsa-211106 could bind to pyruvate carboxylase (PC) by RNA pull down and RNA immunoprecipitation assays and inhibited PC mRNA and protein expression. Our study demonstrates that piR-hsa-211106 inhibits LUAD progression by hindering the expression and function of PC and enhances chemotherapy sensitivity, suggesting that piR-hsa-211106 is a novel diagnostic and therapeutic target for LUAD.

Serum-derived piR-hsa-164586 of extracellular vesicles as a novel biomarker for early diagnosis of non-small cell lung cancer

“…The molecular mechanisms of piRNAs that exert function are largely unclear. A previous study has shown that piR-hsa-211106 inhibits the progression of lung adenocarcinoma and enhances chemotherapy sensitivity by pyruvate carboxylase ( 44 ). piRNAs also work by interacting with piwi proteins and recruiting methyltransferases.…”

Non-Coding RNAs in Pancreatic Cancer Diagnostics and Therapy: Focus on lncRNAs, circRNAs, and piRNAs

“…A recent study showed that piRNA-651 promoted proliferation and migration of breast cancer cells through epigenetic regulation of PTEN promoter inactivation [48]. It was also found that piRNA-211106 could serve as tumor suppressor to inhibit the progression of lung cancer and enhance the chemotherapy sensitivity of cancer cells [49]. In gastric cancer, piRNA-823 was found to be significantly down-regulated and induction of piRNA-823 inhibited cancer cell growth in vitro and in vivo [139].…”

“…Although piRNAs play crucial roles in germ cells and adult stem cells, growing evidences have shown that piRNA and PIWI proteins are involved in tumorigenesis [44][45][46][47]. Recently, more investigations are focused on the roles of piRNAs in cancer development and progression [45,[48][49][50][51]. Because piRNAs regulate gene expression and genome stability in stem cells, any deregulation of piRNAs could cause the development of cancer stem cells and promote cancer progression.…”

Potential roles of PIWI-interacting RNAs in lung cancer

“…The expression of piR-211106 is considerably decreased in NSLCLC tissues compared to normal tissues, indicating that piR-211106 may have an anti-oncogenic effect in lung cancer. A recent research discovered that piR-211106 inhibited pyruvate carboxylase (PC) at the mRNA and protein levels, as well as it directly interacting with the PC protein ( 66 ). The overexpression of piR-211106 results in a decrease in PC expression.…”

“…It was also shown that piR-211106 was associated with treatment resistance in NSCLC cells ( 66 ). They discovered that cells overexpressing piR-211106 were more responsive to cisplatin, a first-line medication for advanced NSCLC.…”